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Review | Open Access

Low back pain and osteoarthritis pain: a perspective of estrogen

Huiwen Pang1,Shihui Chen1,David M. Klyne2David Harrich3Wenyuan Ding4,5Sidong Yang4,5 ( )Felicity Y. Han1 ( )
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia
NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia
Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Department of Spine Surgery, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang 050051, China
Hebei Joint International Research Center for Spinal Diseases, 139 Ziqiang Road, Shijiazhuang 050051, China

These authors contributed equally: Huiwen Pang, Shihui Chen.

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Abstract

Low back pain (LBP) is the world’s leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is amplified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.

References

1

Nicolson, P. J. A. et al. Interventions to increase adherence to therapeutic exercise in older adults with low back pain and/or hip/knee osteoarthritis: a systematic review and meta-analysis. Br. J. Sports Med. 51, 791–799 (2017).

2

Fatoye, F., Gebrye, T. & Odeyemi, I. Real-world incidence and prevalence of low back pain using routinely collected data. Rheumatol. Int. 39, 619–626 (2019).

3

Will, J. S., Bury, D. C. & Miller, J. A. Mechanical low back pain. Am. Fam. Physician 98, 421–428 (2018).

4

Jiang, J. W. et al. Up-regulation of TRAF2 inhibits chondrocytes apoptosis in lumbar facet joint osteoarthritis. Biochem. Biophys. Res. Co. 503, 1659–1665 (2018).

5

Diwan, A. D. & Melrose, J. Intervertebral disc degeneration and how it leads to low back pain. JOR Spine 6, e1231 (2023).

6

Hoy, D. et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 64, 2028–2037 (2012).

7

Hunter, D. J., McDougall, J. J. & Keefe, F. J. The symptoms of osteoarthritis and the genesis of pain. Rheum. Dis. Clin. North Am. 34, 623–643 (2008).

8

Wu, A. et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann. Transl. Med. 8, 299 (2020).

9

Wáng, Y. X., Wáng, J. Q. & Káplár, Z. Increased low back pain prevalence in females than in males after menopause age: evidences based on synthetic literature review. Quant. Imaging Med. Surg. 6, 199 (2016).

10

Dulay, G. S., Cooper, C. & Dennison, E. M. Knee pain, knee injury, knee osteoarthritis & work. Best. Pr. Res. Clin. Rheumatol. 29, 454–461 (2015).

11

Chidi-Ogbolu, N. & Baar, K. Effect of estrogen on musculoskeletal performance and injury risk. Front. Physiol. 9, 1834 (2018).

12

Richardson, H. et al. Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial. Menopause 27, 693–700 (2020).

13

Dedicação, A. C. et al. Prevalence of musculoskeletal pain in climacteric women of a Basic Health Unit in São Paulo/SP. Rev. dor 18, 212–216 (2017).

14

Gibson, C. J., Li, Y., Bertenthal, D., Huang, A. J. & Seal, K. H. Menopause symptoms and chronic pain in a national sample of midlife women veterans. Menopause 26, 708–713 (2019).

15

Klyne, D. M. et al. Cohort profile: why do people keep hurting their back? BMC Res. Notes 13, 538 (2020).

16

Klyne, D. M., Barbe, M. F., James, G. & Hodges, P. W. Does the interaction between local and systemic inflammation provide a link from psychology and lifestyle to tissue health in musculoskeletal conditions? Int. J. Mol. Sci. 22, 7299 (2021).

17

Vergroesen, P. P. A. et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthr. Cartil. 23, 1057–1070 (2015).

18

Millecamps, M. & Stone, L. S. Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice. Pain 159, 1843–1855 (2018).

19

Erwin, W. M. & Hood, K. E. The cellular and molecular biology of the intervertebral disc: a clinician’s primer. J. Can. Chiropr. Assoc. 58, 246–257 (2014).

20

Ghannam, M. et al. Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs. Clin. Anat. 30, 251–266 (2017).

21

De Geer, C. M. Intervertebral disk nutrients and transport mechanisms in relation to disk degeneration: a narrative literature review. J. Chiropr. Med. 17, 97–105 (2018).

22

Kim, J. H., Ham, C. H. & Kwon, W. K. Current knowledge and future therapeutic prospects in symptomatic intervertebral disc degeneration. Yonsei Med. J. 63, 199–210 (2022).

23

Oichi, T., Taniguchi, Y., Oshima, Y., Tanaka, S. & Saito, T. Pathomechanism of intervertebral disc degeneration. JOR Spine 3, e1076 (2020).

24

Gruber, H. E. & Hanley, E. N. Analysis of aging and degeneration of the human intervertebral disc-Comparison of surgical specimens with normal controls. Spine 23, 751–757 (1998).

25

Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H. & Vijg, J. Aging and genome maintenance: lessons from the mouse? Science 299, 1355–1359 (2003).

26

Sadowska, A. et al. Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of proinflammatory cytokine and TRP channel expression. Eur. Spine J. 27, 564–577 (2018).

27

latridis, J. C., Godburn, K., Wuertz, K., Alini, M. & Roughley, P. J. Region-dependent aggrecan degradation patterns in the rat intervertebral disc are affected by mechanical loading in vivo. Spine 36, 203–209 (2011).

28

Gellhorn, A. C., Katz, J. N. & Suri, P. Osteoarthritis of the spine: the facet joints. Nat. Rev. Rheumatol. 9, 216–224 (2013).

29

Suri, P., Hunter, D. J., Rainville, J., Guermazi, A. & Katz, J. N. Presence and extent of severe facet joint osteoarthritis are associated with back pain in older adults. Osteoarthr. Cartil. 21, 1199–1206 (2013).

30

Morris, M., Pellow, J., Solomon, E. M. & Tsele-Tebakang, T. Physiotherapy and a homeopathic complex for chronic low-back pain due to osteoarthritis: a randomized, controlled pilot study. Alter. Ther. Health Med. 22, 48–56 (2016).

31
Lindsey, T. & Dydyk, A. M. in StatPearls (2023).
32

O’Leary, S. A. et al. Facet joints of the spine: structure-function relationships, problems and treatments, and the potential for regeneration. Annu. Rev. Biomed. Eng. 20, 145–170 (2018).

33

Caelers, I. J. et al. Lumbar intervertebral motion analysis during flexion and extension cinematographic recordings in healthy male participants: protocol. JMIR Res. Protoc. 9, e14741 (2020).

34

Vina, E. R. & Kwoh, C. K. Epidemiology of osteoarthritis: literature update. Curr. Opin. Rheumatol. 30, 160–167 (2018).

35

Glyn-Jones, S. et al. Osteoarthritis. Lancet 386, 376–387 (2015).

36

Chen, D. et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 5, 16044 (2017).

37

Alpay-Kanitez, N., Celik, S. & Bes, C. Polyarthritis and its differential diagnosis. Eur. J. Rheumatol. 6, 167–173 (2019).

38

Prieto-Alhambra, D. et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann. Rheum. Dis. 73, 1659–1664 (2014).

39

Murphy, L. B. et al. One in four people may develop symptomatic hip osteoarthritis in his or her lifetime. Osteoarthr. Cartil. 18, 1372–1379 (2010).

40

Losina, E. et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res. 65, 703–711 (2013).

41

Glass, N. et al. Examining sex differences in knee pain: the multicenter osteoarthritis study. Osteoarthr. Cartil. 22, 1100–1106 (2014).

42

Belachew, E. B. & Sewasew, D. T. Molecular mechanisms of endocrine resistance in estrogen-positive breast cancer. Front. Endocrinol. 12, 599586 (2021).

43

Cauley, J. A. Estrogen and bone health in men and women. Steroids 99, 11–15 (2015).

44

Nilsson, S. & Gustafsson, J. Å. Estrogen receptors: therapies targeted to receptor subtypes. Clin. Pharm. Ther. 89, 44–55 (2011).

45

Pöllänen, E. et al. Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre‐ and postmenopausal women. Aging Cell 10, 650–660 (2011).

46

Ali, E. S., Mangold, C. & Peiris, A. N. Estriol: emerging clinical benefits. Menopause 24, 1081–1085 (2017).

47

Kumar, R. S. & Goyal, N. Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology. Life Sci. 269, 119091 (2021).

48

Emmanuelle, N. E. et al. Critical role of estrogens on bone homeostasis in both male and female: from physiology to medical implications. Int. J. Mol. Sci. 22, 1568 (2021).

49

Khosla, S., Oursler, M. J. & Monroe, D. G. Estrogen and the skeleton. Trends Endocrinol. Metab. 23, 576–581 (2012).

50

Levin, E. R. Extranuclear steroid receptors are essential for steroid hormone actions. Annu. Rev. Med. 66, 271–280 (2015).

51

Roman-Blas, J. A., Castaneda, S., Largo, R. & Herrero-Beaumont, G. Osteoarthritis associated with estrogen deficiency. Arthritis Res. Ther. 11, 241 (2009).

52

Song, X. X. et al. Estrogen receptor expression in lumbar intervertebral disc of the elderly: gender- and degeneration degree-related variations. Jt. Bone Spine 81, 250–253 (2014).

53

Song, X. X., Shi, S., Guo, Z., Li, X. F. & Yu, B. W. Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: Colocalization and correlation with the expression of Substance P in nucleus pulposus. Oncotarget 8, 38136–38144 (2017).

54

Wei, A. Q. et al. Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc. J. Steroid Biochem. 158, 46–55 (2016).

55

Dreier, R., Ising, T., Ramroth, M. & Rellmann, Y. Estradiol inhibits ER stress-induced apoptosis in chondrocytes and contributes to a reduced osteoarthritic cartilage degeneration in female mice. Front. Cell Dev. Biol. 10, 913118 (2022).

56

Braidman, I. P. et al. Localization of estrogen receptor β protein expression in adult human bone. J. Bone Min. Res. 16, 214–220 (2001).

57

Dietrich, W. et al. Estrogen Receptor-β Is the Predominant Estrogen Receptor Subtype in Normal Human Synovia. J. Soc. Gynecol. Investig. 13, 512–517 (2006).

58

Hang, X. et al. Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis. J. Inflamm. Res. 14, 843–858 (2021).

59

Maneix, L. et al. 17Beta-oestradiol up-regulates the expression of a functional UDP-glucose dehydrogenase in articular chondrocytes: comparison with effects of cytokines and growth factors. Rheumatology. 47, 281–288 (2008).

60

Claassen, H., Schünke, M. & Kurz, B. Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage. Cell Tissue Res. 319, 439–445 (2005).

61

Christgau, S. et al. Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM). Menopause 11, 508–518 (2004).

62

Oestergaard, S. et al. Effects of ovariectomy and estrogen therapy on type Ⅱ collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation. Arthritis Rheum. 54, 2441–2451 (2006).

63

SILBERBERG, M. & SILBERBERG, R. Modifying action of estrogen on the evolution of osteoarthrosis in mice of different ages. Endocrinology 72, 449–451 (1963).

64

Tsai, C. L. & Liu, T. K. Estradiol-induced knee osteoarthrosis in ovariectomized rabbits. Clin. Orthop. Relat. Res. 291, 295–302 (1993).

65

Rosner, I. A. et al. Pathologic and metabolic responses of experimental osteoarthritis to estradiol and an estradiol antagonist. Clin. Orthop. Relat. Res. 171, 280–286 (1982).

66

Ha, K. Y. et al. Expression of estrogen receptor of the facet joints in degenerative spondylolisthesis. Spine 30, 562–566 (2005).

67

Wang, T., Zhang, L., Huang, C., Cheng, A. G. & Dang, G. T. Relationship between osteopenia and lumbar intervertebral disc degeneration in ovariectomized rats. Calcif. Tissue Int. 75, 205–213 (2004).

68

Liu, Q. et al. Estrogen deficiency exacerbates intervertebral disc degeneration induced by spinal instability in rats. Spine 44, E510–E519 (2019).

69

Jin, L. Y. et al. Estradiol alleviates intervertebral disc degeneration through modulating the antioxidant enzymes and inhibiting autophagy in the model of menopause rats. Oxid. Med. Cell Longev. 2018, 7890291 (2018).

70

Jia, H. et al. Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity. Sci. Rep. 6, 27521 (2016).

71

Xiao, Z. F. et al. Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice. Arthritis Res. Ther. 20, 207 (2018).

72

Sheng, B. et al. Protective effect of estrogen against calcification in the cartilage endplate. Int. J. Clin. Exp. Pathol. 11, 1660–1666 (2018).

73

Shelby, T. et al. The role of sex hormones in degenerative disc disease. Global Spine J, 21925682231152826 (2023).

74

Kupka, J. et al. Adrenoceptor expression during intervertebral disc degeneration. Int. J. Mol. Sci. 21, 2085 (2020).

75

Wu, T. et al. Three-dimensional visualization and pathologic characteristics of cartilage and subchondral bone changes in the lumbar facet joint of an ovariectomized mouse model. Spine J. 18, 663–673 (2018).

76

Gou, Y. et al. Salmon calcitonin attenuates degenerative changes in cartilage and subchondral bone in lumbar facet joint in an experimental rat model. Med. Sci. Monit. 24, 2849–2857 (2018).

77

Chen, H., Zhu, H., Zhang, K., Chen, K. & Yang, H. Estrogen deficiency accelerates lumbar facet joints arthritis. Sci. Rep. 7, 1379 (2017).

78

Zhao, Y. et al. Lumbar disk degeneration in female patients with and without ovariectomy: a case-control study. World Neurosurg. 156, 68–75 (2021).

79

Ketut, I. Suyasa*, I. G. N. Y. S. The role of aging, body mass index and estrogen on symptomatic lumbar osteoarthritis in post-menopausal women. Int. J. Res. Med. Sci. 4, 1325 (2016).

80

Xu, X. et al. Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med. Sci. Monit. 25, 3146–3153 (2019).

81

Jiang, A. et al. Phenotype changes of subchondral plate osteoblasts based on a rat model of ovariectomy-induced osteoarthritis. Ann. Transl. Med. 8, 476 (2020).

82

Høegh-Andersen, P. et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res. Ther. 6, R169–R180 (2004).

83

Hashem, G. et al. Relaxin and beta-estradiol modulate targeted matrix degradation in specific synovial joint fibrocartilages: progesterone prevents matrix loss. Arthritis Res. Ther. 8, R98 (2006).

84

Turner, A. S., Athanasiou, K. A., Zhu, C. F., Alvis, M. R. & Bryant, H. U. Biochemical effects of estrogen on articular cartilage in ovariectomized sheep. Osteoarthr. Cartil. 5, 63–69 (1997).

85

Dai, G., Wang, S., Li, J., Liu, C. & Liu, Q. The validity of osteoarthritis model induced by bilateral ovariectomy in guinea pig. J. Huazhong Univ. Sci. Technol. Med. Sci. 26, 716–719 (2006).

86

Sniekers, Y. H., Weinans, H., Bierma-Zeinstra, S. M., van Leeuwen, J. P. & van Osch, G. J. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment - a systematic approach. Osteoarthr. Cartil. 16, 533–541 (2008).

87

Lu, Z. H., Zhang, A. H., Wang, J. C., Han, K. J. & Gao, H. Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage. BMC Musculoskelet. Disord. 23, 685 (2022).

88

Srikanth, V. K. et al. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthr. Cartil. 13, 769–781 (2005).

89

Liu, S. et al. 17β-Estradiol inhibits intervertebral disc degeneration by down-regulating MMP-3 and MMP-13 and up-regulating type Ⅱ collagen in a rat model. Artif. Cells Nanomed. Biotechnol. 46, 182–191 (2018).

90

Wang, H. et al. 17β-Estradiol alleviates intervertebral disc degeneration by inhibiting NF-κB signal pathway. Life Sci. 284, 119874 (2021).

91

Song, X. X., Jin, L. Y., Li, X. F., Luo, Y. & Yu, B. W. Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc. Inflammation 44, 506–517 (2020).

92

Baron, Y. M., Brincat, M. P., Galea, R. & Calleja, N. Intervertebral disc height in treated and untreated overweight post-menopausal women. Hum. Reprod. 20, 3566–3570 (2005).

93

Marty-Poumarat, C., Scattin, L., Marpeau, M., Garreau De Loubresse, C. & Aegerter, P. Natural history of progressive adult scoliosis. Spine 32, 1227–1234 (2007).

94

Marty-Poumarat, C. et al. Does hormone replacement therapy prevent lateral rotatory spondylolisthesis in postmenopausal women? Eur. Spine J. 21, 1127–1134 (2011).

95

Muscat Baron, Y., Brincat, M. P., Galea, R. & Calleja, N. Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures. Climacteric 10, 314–319 (2007).

96

Park, J. H., Hong, J. Y., Han, K., Han, S. W. & Chun, E. M. Relationship between hormone replacement therapy and spinal osteoarthritis: a nationwide health survey analysis of the elderly Korean population. BMJ Open 7, e018063 (2017).

97

Cheung, P., Gossec, L. & Dougados, M. What are the best markers for disease progression in osteoarthritis (OA)? Best. Pr. Res. Clin. Rheumatol. 24, 81–92 (2010).

98

Yasuoka, T., Nakashima, M., Okuda, T. & Tatematsu, N. Effect of estrogen replacement on temporomandibular joint remodeling in ovariectomized rats. J. Oral. Maxillofac. Surg. 58, 189–196 (2000).

99

Abdrabuh, A., Baljon, K. & Alyami, Y. Impact of estrogen therapy on temporomandibular joints of rats: Histological and hormone analytical study. Saudi Dent. J. 33, 608–613 (2021).

100

Torres-Chávez, K. E. et al. Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Eur. J. Pain. 16, 204–216 (2011).

101

Fischer, L. et al. The Influence of Sex and Ovarian Hormones on Temporomandibular Joint Nociception in Rats. J. Pain. 9, 630–638 (2008).

102

Ham, K. D., Loeser, R. F., Lindgren, B. R. & Carlson, C. S. Effects of long‐term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. Arthritis Rheum. 46, 1956–1964 (2002).

103

Schmidt, I. U., Wakley, G. K. & Turner, R. T. Effects of Estrogen and Progesterone on Tibia Histomorphometry in Growing Rats. Calcif. Tissue Int. 67, 47–52 (2000).

104

Chlebowski, R. T. et al. Estrogen alone and joint symptoms in the Women’s Health Initiative randomized trial. Menopause 25, 1313 (2018).

105

Jung, J. H. et al. Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study. Menopause 26, 598–602 (2018).

106

Wluka, A. E., Davis, S. R., Bailey, M., Stuckey, S. & Cicuttini, F. Users of oestrogen replacement therapy have more knee cartilage than non-users. Ann. Rheum. Dis. 60, 332–336 (2001).

107

Spector, T. D., Nandra, D., Hart, D. J. & Doyle, D. V. Is hormone replacement therapy protective for hand and knee osteoarthritis in women?: The Chingford study. Ann. Rheum. Dis. 56, 432–434 (1997).

108

Cirillo, D. J., Wallace, R. B., Wu, L. & Yood, R. A. Effect of hormone therapy on risk of hip and knee joint replacement in the Women’s Health Initiative. Arthritis Rheum. 54, 3194–3204 (2006).

109

Yang, S. D., Zhang, F., Ma, J. T. & Ding, W. Y. Intervertebral disc ageing and degeneration: The antiapoptotic effect of oestrogen. Ageing Res. Rev. 57, 100978 (2020).

110

Chen, Q., Zhang, W., Sadana, N. & Chen, X. Estrogen receptors in pain modulation: cellular signaling. Biol. Sex. Differ. 12, 22 (2021).

111

Sun, L. H. et al. Estrogen modulation of visceral pain. J. Zhejiang Univ. Sci. B 20, 628–636 (2019).

112

Xunlu, Y. et al. Integrative bioinformatics analysis reveals potential gene biomarkers and analysis of function in human degenerative disc annulus fibrosus cells. Biomed. Res. Int. 2019, 9890279 (2019).

113

Huang, Y. C., Urban, J. P. & Luk, K. D. Intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol. 10, 561–566 (2014).

114

Grunhagen, T. D., Shirazi-Adl, A., Fairbank, J. C. & Urban, J. P. Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites. Orthop. Clin. North Am. 42, 465–477 (2011).

115

Stephan, S., Johnson, W. E. & Roberts, S. The influence of nutrient supply and cell density on the growth and survival of intervertebral disc cells in 3D culture. Eur. Cell Mater. 22, 97–108 (2011).

116

Adams, M. A., Dolan, P. & McNally, D. S. The internal mechanical functioning of intervertebral discs and articular cartilage, and its relevance to matrix biology. Matrix Biol. 28, 384–389 (2009).

117

Zhang, F. A. N., Zhao, X., Shen, H. & Zhang, C. Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int. J. Mol. Med. 37, 1439–1448 (2016).

118

Zhou, G. Q., Yang, F., Leung, V. V. L. & Cheung, K. M. C. (v) Molecular and cellular biology of the intervertebral disc and the use of animal models. Curr. Orthop. 22, 267–273 (2008).

119

Le Maitre, C. L., Freemont, A. J. & Hoyland, J. A. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res. Ther. 9, R45 (2007).

120

Roberts, S., Evans, H., Trivedi, J. & Menage, J. Histology and pathology of the human intervertebral disc. J. Bone Jt. Surg. Am. 88, 10–14 (2006).

121

Kepler, C. K. M. D. M. B. A., Ponnappan, R. K. M. D., Tannoury, C. A. M. D., Risbud, M. V. P. & Anderson, D. G. M. D. The molecular basis of intervertebral disc degeneration. Spine J. 13, 318–330 (2013).

122

Xu, Y. Q., Zhang, Z. H., Zheng, Y. F. & Feng, S. Q. Dysregulated miR-133a mediates loss of type ii collagen by directly targeting matrix metalloproteinase 9 (mmp9) in human intervertebral disc degeneration. Spine 41, E717–E724 (2016).

123

Zawilla, N. H. et al. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration. J. Occup. Rehabil. 24, 370–381 (2013).

124

Molinos, M. et al. Inflammation in intervertebral disc degeneration and regeneration. J. R. Soc. Interface 12, 20150429 (2015).

125

Lee, S. et al. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clin. Biochem. 42, 1504–1511 (2009).

126

Currò, M. et al. Differential expression of transglutaminase genes in patients with chronic periodontitis. Oral. Dis. 20, 616–623 (2014).

127

Le Maitre, C. L., Freemont, A. J. & Hoyland, J. A. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res. Ther. 7, R732–R745 (2005).

128

Johnson, Z. I., Schoepflin, Z. R., Choi, H., Shapiro, I. M. & Risbud, M. V. Disc in flames: Roles of TNF-alpha and IL-1beta in intervertebral disc degeneration. Eur. Cell Mater. 30, 104–117 (2015).

129

Gu, S. X. et al. MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc. Gene 555, 80–87 (2015).

130

Mavrogonatou, E., Angelopoulou, M. T. & Kletsas, D. The catabolic effect of TNFα on bovine nucleus pulposus intervertebral disc cells and the restraining role of glucosamine sulfate in the TNFα-mediated up-regulation of MMP-3. J. Orthop. Res. 32, 1701–1707 (2014).

131

Yao, Z. et al. Salubrinal Suppresses IL-17-Induced Upregulation of MMP-13 and Extracellular Matrix Degradation Through the NF-kB Pathway in Human Nucleus Pulposus Cells. Inflammation 39, 1997–2007 (2016).

132

Yang, S. D., Ma, L., Yang, D. L. & Ding, W. Y. Combined effect of 17 beta-estradiol and resveratrol against apoptosis induced by interleukin-1 beta in rat nucleus pulposus cells via PI3K/Akt/caspase-3 pathway. PeerJ 4, e1640 (2016).

133

Song, M. et al. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage. Biomed. Pharmacother. 84, 1137–1143 (2016).

134

Yang, S. D. et al. 17β-Estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13. Apoptosis 20, 348–357 (2015).

135

Gao, X. W., Su, X. T., Lu, Z. H. & Ou, J. 17β-Estradiol prevents extracellular matrix degradation by downregulating MMP3 expression via PI3K/Akt/FOXO3 pathway. Spine 45, 292–299 (2020).

136

Shen, C., Yan, J., Jiang, L. S. & Dai, L. Y. Autophagy in rat annulus fibrosus cells: evidence and possible implications. Arthritis Res. Ther. 13, R132 (2011).

137

Yang, D. et al. 17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition. Biomed. Pharmacother. 107, 1004–1009 (2018).

138

Li, P. et al. 17beta-estradiol attenuates TNF-alpha-induced premature senescence of nucleus pulposus cells through regulating the ROS/NF-kappaB pathway. Int. J. Biol. Sci. 13, 145–156 (2017).

139

Lin, C. Y., Chen, J. H., Fu, R. H. & Tsai, C. W. Induction of Pi form of glutathione S‑transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity. Chem. Res. Toxicol. 27, 1958–1966 (2014).

140

Huang, H., Zhong, R., Xia, Z., Song, J. & Feng, L. Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways. Molecules 19, 11196–11210 (2014).

141

Kim, D. E., Kim, B., Shin, H. S., Kwon, H. J. & Park, E. S. The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway. Exp. Cell Res. 327, 264–275 (2014).

142

Musumeci, G. et al. Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: A morphological study. Int. J. Mol. Sci. 14, 15767–15784 (2013).

143

Cravero, J. D. et al. Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin‐like growth factor 1–mediated cell survival and proteoglycan synthesis. Arthritis Rheum. 60, 492–500 (2009).

144

Guo, F., Zou, Y. & Zheng, Y. Moracin M inhibits lipopolysaccharide-induced inflammatory responses in nucleus pulposus cells via regulating PI3K/Akt/mTOR phosphorylation. Int. Immunopharmacol. 58, 80–86 (2018).

145

Liu, H. et al. Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells. Mol. Med. Rep. 16, 1093–1100 (2017).

146

Wang, T. et al. 17β-Estradiol inhibites tumor necrosis factor-α induced apoptosis of human nucleus pulposus cells via the PI3K/Akt pathway. Med. Sci. Monit. 22, 4312–4322 (2016).

147

Guo, H. T. et al. 17beta‑Estradiol protects against interleukin‑1beta‑induced apoptosis in rat nucleus pulposus cells via the mTOR/caspase‑3 pathway. Mol. Med. Rep. 20, 1523–1530 (2019).

148

Kim, J. et al. Syringaresinol reverses age-related skin atrophy by suppressing FoxO3a-mediated matrix metalloproteinase–2 activation in Copper/Zinc superoxide dismutase–deficient mice. J. Investig. Dermatol. 139, 648–655 (2019).

149

Li, P. et al. Osmolarity affects matrix synthesis in the nucleus pulposus associated with the involvement of MAPK pathways: A study of ex vivo disc organ culture system. J. Orthop. Res. 34, 1092–1100 (2016).

150

Li, P. et al. Estrogen enhances matrix synthesis in nucleus pulposus cell through the estrogen receptor β-p38 MAPK pathway. Cell Physiol. Biochem. 39, 2216–2226 (2016).

151

Lisowska, B., Lisowski, A. & Siewruk, K. Substance P and chronic pain in patients with chronic inflammation of connective tissue. PLoS One 10, e0139206 (2015).

152

Wu, S. et al. Occurrence of substance P and neurokinin receptors during the early phase of spinal fusion. Mol. Med. Rep. 17, 6691–6696 (2018).

153

Zieglgansberger, W. Substance P and pain chronicity. Cell Tissue Res. 375, 227–241 (2019).

154

Zheng, J. et al. Reactive oxygen species mediate low back pain by upregulating substance P in intervertebral disc degeneration. Oxid. Med. Cell Longev. 2021, 6681815 (2021).

155

Martinez, A. N. & Philipp, M. T. Substance P and antagonists of the neurokinin-1 receptor in neuroinflammation associated with infectious and neurodegenerative diseases of the central nervous system. J. Neurol. Neuromed. 1, 29–36 (2016).

156

Ho, W. Z. & Douglas, S. D. Substance P and neurokinin-1 receptor modulation of HIV. J. Neuroimmunol. 157, 48–55 (2004).

157

Bost, K. L. Tachykinin-mediated modulation of the immune response. Front. Biosci. 9, 3331–3332 (2004).

158

Wang, H. et al. Different concentrations of 17β-estradiol modulates apoptosis induced by interleukin-1β in rat annulus fibrosus cells. Mol. Med. Rep. 10, 2745–2751 (2014).

159

Zhao, C. M. et al. 17β-Estradiol protects rat annulus fibrosus cells against apoptosis via α1 integrin-mediated adhesion to type I collagen: an in-vitro study. Med. Sci. Monit. 22, 1375–1383 (2016).

160

Ni, B. B. et al. The effect of transforming growth factor beta1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation. Cytokine 70, 87–96 (2014).

161

Bai, Z. L. et al. Toxic effects of levofloxacin on rat annulus fibrosus cells: an in-vitro study. Med. Sci. Monit. 20, 2205–2212 (2014).

162

Wei, H. K. et al. Levofloxacin increases apoptosis of rat annulus fibrosus cells via the mechanism of upregulating MMP-2 and MMP-13. Int. J. Clin. Exp. Med. 8, 20198–20207 (2015).

163

Pang, L., Yang, K. & Zhang, Z. High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress. Biosci. Rep. 40, BSR20200262 (2020).

164

Madiraju, P., Gawri, R., Wang, H., Antoniou, J. & Mwale, F. Mechanism of parathyroid hormone-mediated suppression of calcification markers in human intervertebral disc cells. Eur. Cell Mater. 25, 268–283 (2013).

165

Yang, S. D. et al. 17β-Estradiol protects against apoptosis induced by levofloxacin in rat nucleus pulposus cells by upregulating integrin α2β1. Apoptosis 19, 789–800 (2014).

166

Peng, B. & Li, Y. Concerns about cell therapy for intervertebral disc degeneration. NPJ Regen. Med. 7, 46 (2022).

167

Sheng, B. et al. Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor α. Acta Biochim. Biophys. Sin. 50, 345–354 (2018).

168

Han, Y. et al. Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-kappaB pathway: implications for disc degeneration. Biochem. Biophys. Res. Commun. 516, 1026–1032 (2019).

169

Jiang, Z. et al. High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells. J. Orthop. Res. 36, 2476–2483 (2018).

170

Ding, L. et al. Effects of CCN3 on rat cartilage endplate chondrocytes cultured under serum deprivation in vitro. Mol. Med. Rep. 13, 2017–2022 (2016).

171

Li, D. et al. Role of the mitochondrial pathway in serum deprivation-induced apoptosis of rat endplate cells. Biochem. Biophys. Res. Commun. 452, 354–360 (2014).

172

Walsh, D. A. et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology 49, 1852–1861 (2010).

173

Donell, S. Subchondral bone remodelling in osteoarthritis. EFORT Open Rev. 4, 221–229 (2019).

174

Yuan, X. L. et al. Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies. Osteoarthr. Cartil. 22, 1077–1089 (2014).

175

Grassel, S., Zaucke, F. & Madry, H. Osteoarthritis: novel molecular mechanisms increase our understanding of the disease pathology. J. Clin. Med. 10, 1938 (2021).

176

Aso, K. et al. Time course and localization of nerve growth factor expression and sensory nerve growth during progression of knee osteoarthritis in rats. Osteoarthr. Cartil. 30, 1344–1355 (2022).

177

Rockel, J. S. & Kapoor, M. Autophagy: controlling cell fate in rheumatic diseases. Nat. Rev. Rheumatol. 13, 193 (2017).

178

Gwinn, D. M. et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. cell 30, 214–226 (2008).

179

Liu-Bryan, R. & Terkeltaub, R. Emerging regulators of the inflammatory process in osteoarthritis. Nat. Rev. Rheumatol. 11, 35–44 (2015).

180

Mei, R. et al. 17β-Estradiol induces mitophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR signaling pathway. Front. Endocrinol. (Lausanne) 11, 615250 (2021).

181

Matsuzaki, T. et al. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann. Rheum. Dis. 73, 1397–1404 (2014).

182

Zhang, Z. et al. Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway. J. Cell Mol. Med. 23, 177–193 (2019).

183

Montagnoli, C. et al. β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis. Biol. Chem. 398, 1045–1054 (2017).

184

Yu, X. et al. NGF increases FGF2 expression and promotes endothelial cell migration and tube formation through PI3K/Akt and ERK/MAPK pathways in human chondrocytes. Osteoarthr. Cartil. 27, 526–534 (2019).

185

Huang, J. G. et al. 17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway. Cell Mol. Biol. Lett. 16, 564–575 (2011).

186

Shang, X., Zhang, L., Jin, R., Yang, H. & Tao, H. Estrogen regulation of the expression of pain factor NGF in rat chondrocytes. J. Pain. Res. 14, 931–940 (2021).

187

Musgrave, D. S., Vogt, M. T., Nevitt, M. C. & Cauley, J. A. Back problems among postmenopausal women taking estrogen replacement therapy: The study of osteoporotic fractures. Spine 26, 1606–1612 (2001).

188

Brynhildsen, J. O., Björs, E., Skarsgård, C. & Hammar, M. L. Is hormone replacement therapy a risk factor for low back pain among postmenopausal women? Spine 23, 809–813 (1998).

189

Heuch, I., Heuch, I., Hagen, K., Storheim, K. & Zwart, J. A. Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study. BMC Musculoskelet. Disord. 24, 84 (2023).

190
Ortmann, O. & Lattrich, C. The treatment of climacteric symptoms. Dtsch Arztebl Int. 109, 316–323 (2012). quiz 324.
191

Smith, Y. R. et al. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J. Neurosci. 26, 5777–5785 (2006).

192

Hannan, M. T., Felson, D. T., Anderson, J. J., Naimark, A. & Kannel, W. B. Estrogen use and radiographic osteoarthritis of the knee in women. The Framingham Osteoarthritis Study. Arthritis Rheum. 33, 525–532 (1990).

193

Zhang, Y. et al. Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study. Arthritis Rheum. 41, 1867–1873 (1998).

194

Kwan Tat, S., Lajeunesse, D., Pelletier, J. P. & Martel-Pelletier, J. Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best. Pr. Res Clin. Rheumatol. 24, 51–70 (2010).

195

Burr, D. B. & Gallant, M. A. Bone remodelling in osteoarthritis. Nat. Rev. Rheumatol. 8, 665–673 (2012).

196

Kou, X. X. et al. 17beta-estradiol aggravates temporomandibular joint inflammation through the NF-kappaB pathway in ovariectomized rats. Arthritis Rheum. 63, 1888–1897 (2011).

197

Rossouw, J. E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288, 321–333 (2002).

198

Miller, V. M. & Harman, S. M. An update on hormone therapy in postmenopausal women: mini-review for the basic scientist. Am. J. Physiol.-Heart C. 313, H1013–H1021 (2017).

199

Canonico, M. et al. Hormone therapy and venous thromboembolism among postmenopausal women - Impact of the route of estrogen administration and progestogens: The ESTHER study. Circulation 115, 840–845 (2007).

200

Patel, S., Homaei, A., Raju, A. B. & Meher, B. R. Estrogen: the necessary evil for human health, and ways to tame it. Biomed. Pharmacother. 102, 403–411 (2018).

201

LaCroix, A. Z. et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial EDITORIAL COMMENT. Obstet. Gynecol. Surv. 66, 427–429 (2011).

202

Goldstein, S. R. Selective estrogen receptor modulators and bone health. Climacteric 25, 56–59 (2022).

203

Desmawati, D. & Sulastri, D. Phytoestrogens and their health effect. Open Access Maced. J. Med Sci. 7, 495–499 (2019).

204

Li, X. et al. The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine 33, 2586–2595 (2008).

205

Lewis, J. S. & Jordan, V. C. Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance. Mutat. Res. 591, 247–263 (2005).

206

Lugo, L., Villalvilla, A., Largo, R., Herrero-Beaumont, G. & Roman-Blas, J. A. Selective estrogen receptor modulators (SERMs): new alternatives for osteoarthritis? Maturitas 77, 380–384 (2014).

207

Downton, T., Zhou, F., Segara, D., Jeselsohn, R. & Lim, E. Oral selective estrogen receptor degraders (SERDs) in breast cancer: advances, challenges, and current status. Drug Des. Devel. Ther. 16, 2933–2948 (2022).

208

Deng, Y., Li, L., Li, C., Wang, F. & Qu, Y. Efficacy of combined medication of risedronate sodium and selective estrogen receptor modulator on the postmenopausal osteoporosis. Pak. J. Pharm. Sci. 33, 495–498 (2020).

209

Wilcox, N. S. et al. Sex-specific cardiovascular risks of cancer and its therapies. Circ. Res. 130, 632–651 (2022).

210

Bhadouria, N., Berman, A. G., Wallace, J. M. & Holguin, N. Raloxifene stimulates estrogen signaling to protect against age- and sex-related intervertebral disc degeneration in mice. Front. Bioeng. Biotechnol. 10, 924918 (2022).

211

Chen, M. N., Lin, C. C. & Liu, C. F. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric 18, 260–269 (2015).

212

Lagari, V. S. & Levis, S. Phytoestrogens and bone health. Curr. Opin. Endocrinol. Diabetes Obes. 17, 546–553 (2010).

213

Chudzinska, M. et al. Resveratrol and cardiovascular system-the unfulfilled hopes. Ir. J. Med Sci. 190, 981–986 (2021).

214

Gilmer, G. et al. Uncovering the “riddle of femininity” in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment. Osteoarthr. Cartil. 31, 447–457 (2023).

215

Kyllönen, E. S., Väänänen, H. K., Vanharanta, J. H. V. & Heikkinen, J. E. Influence of estrogen-progestin treatment on back pain and disability among slim premenopausal women with low lumbar spine bone mineral density: A 2-year placebo-controlled randomized trial. Spine (Philos. Pa 1976) 24, 704–708 (1999).

216

Yang, J. H., Kim, J. H., Lim, D. S. & Oh, K. J. Effect of combined sex hormone replacement on bone/cartilage turnover in a murine model of osteoarthritis. Clin. Orthop. Surg. 4, 234–241 (2012).

Bone Research
Article number: 42
Cite this article:
Pang H, Chen S, Klyne DM, et al. Low back pain and osteoarthritis pain: a perspective of estrogen. Bone Research, 2023, 11: 42. https://doi.org/10.1038/s41413-023-00280-x

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Received: 14 December 2022
Revised: 28 June 2023
Accepted: 10 July 2023
Published: 04 August 2023
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