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Original Article | Open Access

Fragile X Messenger Ribonucleoprotein 1 (FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice

Padmini Deosthale1,2, Julián Balanta-Melo1,2,3,4, Amy Creecy5, Chongshan Liu6, Alejandro Marcial1, Laura Morales1, Julita Cridlin1, Sylvia Robertson1, Chiebuka Okpara1, David J. Sanchez1, Mahdi Ayoubi7, Joaquín N. Lugo8, Christopher J. Hernandez6, Joseph M. Wallace2,3,5, Lilian I. Plotkin1,2,3 ( )
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
Roudebush Veterans Administration Medical Center, Indianapolis, IN, 46202, USA
Indiana Center for Musculoskeletal Health, Indianapolis, IN 46202, USA
Universidad del Valle School of Dentistry, Cali 760043, Colombia
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, 46202 Indianapolis, IN, 46202, USA
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA
Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA
Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA
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Abstract

Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene mutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old (mo) male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown. We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-mo mice. The cancellous bone mass is higher only in females, whereas, cortical bone mass is higher in 2- and 9-mo males, but higher in 2- and lower in 9-mo female FMR1-knockout mice. Furthermore, male bones show higher biomechanical properties at 2mo, and females at both ages. Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro, without affecting osteoclasts in vivo/ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass/strength.

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Bone Research
Volume 11,
December 2023
Article number: 25
DOI: 10.1038/s41413-023-00256-x
Cite this article:
Deosthale P, Balanta-Melo J, Creecy A, et al. Fragile X Messenger Ribonucleoprotein 1 (FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice. Bone Research, 2023, 11: 25. https://doi.org/10.1038/s41413-023-00256-x

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Received: 02 December 2022
Revised: 08 February 2023
Accepted: 01 March 2023
Published: 17 May 2023
© The Author(s) 2023

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