Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.

As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway. Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction.

Single-atom nanozymes (SANs) are the new emerging catalytic nanomaterials with enzyme-mimetic activities, which have many extraordinary merits, such as low-cost preparation, maximum atom utilization, ideal catalytic activity, and optimized selectivity. With these advantages, SANs have received extensive research attention in the fields of chemistry, energy conversion, and environmental purification. Recently, a growing number of studies have shown the great promise of SANs in biological applications. In this article, we present the most recent developments of SANs in anti-infective treatment, cancer diagnosis and therapy, biosensing, and antioxidative therapy. This text is expected to better guide the readers to understand the current state and future clinical possibilities of SANs in medical applications.

Treatment of osteoporosis is still a challenge in clinic, which leads to an increasing social burden as the aging of population. Exosomes originated from human adipose-derived stem cells (hASCs) hold promise to promote osteogenic differentiation, thus may ameliorate osteoporosis. The main purpose of this study was to investigate the novel usage of hASC-derived exosomes in the treatment of osteoporosis and their underlying mechanism. Two types of exosomes, i.e., exosomes derived from hASCs cultured in proliferation medium (P-Exos) and osteogenic induction medium (O-Exos), were obtained. As compared with P-Exos, O-Exos could promote the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) from osteoporotic mice in vitro and ameliorated osteoporosis in vivo. Then, microRNA (miRNA)-335-3p was identified to be the key differentially expressed microRNA between the two exosomes by small RNA sequencing, gene overexpression and knock-down, qRT-PCR, and dual-luciferase reporter assay, and Aplnr was confirmed to be the potential target gene of miRNA-335-3p. In addition, miR-335-3p inhibitor-optimized O-Exos were established by transfection of miR-335-3p inhibitor, which significantly enhanced the osteogenic differentiation of mBMSCs in vitro, and bone density and number of trabecular bones in vivo compared with unoptimized O-Exos. Our results indicated that the ASC-exosome-based therapy brings new possibilities for osteoporosis treatment. Besides, engineered exosomes based on transfection of miRNA are a promising strategy to optimize the therapeutic effect of exosomes on osteoporosis.