BACKGROUND:LPS-inhibited osteoblastic differentiation plays an important role in the pathogenesis of osteomyelitis. Thus, searching for drugs that affect LPS-mediated osteoblastic differentiation may be crucial in developing therapies for osteomyelit...

The mitochondrial unfolded protein response (UPR^mt) is a mitochondrial-to-nuclear signaling pathway that is activated to maintain mitochondrial function when there is an accumulation of misfolded proteins within mitochondria. Mitochondrial function is essential for chondrocyte homeostasis, and mitochondrial dysfunction is a characteristic of osteoarthritis (OA). However, the role of the UPR^mt in OA remains unclear. In the present study, the level of the UPR^mt was examined in primary mouse chondrocytes subjected to different stresses and in the articular cartilage of OA model mice and OA patients. The relationship between UPR^mt activation and OA progression was studied. The UPR^mt was induced in primary mouse chondrocytes subjected to diverse stresses and in the cartilage of OA mice. Enhancement of the UPR^mt with nicotinamide riboside (NR) significantly improved mitochondrial function, reduced chondrocyte death, attenuated OA pain, and ameliorated OA progression, and the protective effects decreased significantly in chondrocyte-specific Atf5 knockout (ATF5^f/fCol2a1-CreER^T2) mice. UPR^mt induction was also identified in the articular cartilage of OA patients and was associated with reduced chondrocyte death, less severe hip pain, and lower levels of inflammation in synovial fluid. These findings identify the induction of the UPR^mt in primary mouse chondrocytes exposed to pathological stresses and in the articular cartilage of OA model mice and OA patients. Enhancement of the UPR^mt ameliorates OA progression, suggesting that the UPR^mt exerts a protective effect against OA and may be a potential diagnostic and therapeutic strategy for OA.

Introduction: Failed back surgery syndrome is a situation where there is failure after lumbar surgery aimed at correcting lumbar disease that is characterized by continuous back and/or leg pain. Epidural fibrosis and adhesions are among the major causes of failed back surgery syndrome. In recent years, several biomaterials have been applied as barriers or deterrents to prevent the compression of neural structures by postsurgical fibrosis. Methods: In this study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of exosomes from human umbilical cord mesenchymal stem cells, was developed. Its structure and morphology, water content, thickness, and mechanical properties of elasticity were analyzed and characterized. The degradation of the BC+exosomes (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on epidural fibrosis post-laminectomy in a rabbit model was investigated. Results: The BC+Exos membrane showed a three-dimensional network structure constituted of high-purity cellulose and moderate mechanical properties. No degeneration was observed. The BC+Exos membrane showed no cytotoxicity and displayed biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis and peridural adhesions. Conclusion: Based on the current findings, the BC+Exos membrane is a promising material to prevent postoperative epidural fibrosis and adhesion.

Hydrogen sulfide (H₂S), a gasotransmitter, plays an important role in the regulation of bone homeostasis. However, the precise effect of H₂S on osteoclasts was still elusive. The goal of this study was to determine the potential role of H₂S in regulation of osteoclasts and the underlying mechanisms by which H₂S affected osteoclastogenesis. The present study applied western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase staining, pit formation assay, immunofluorescence confocal microscopy, transmission electron microscopy, and annexin v-fluorescein isothiocyanate/propidium iodide double-staining assay. The results showed that the expressions of cystathionine b-synthase (CBS) and cystathionine c-lyase (CSE) were obviously increased in osteoclast differentiation induced by the receptor activator of nuclear factor kappa-Β ligand (RANKL). In addition, H₂S promoted RANKL-induced osteoclastogenesis and inhibited apoptosis of mature osteoclasts. Mechanistically, H₂S inhibited autophagy in Raw 264.7 cells. Autophagy activator (rapamycin) alleviated the induction of osteoclast differentiation by H₂S. Further studies showed that H₂S inhibited autophagy by activating the PI3K/AKT/mTOR signaling pathway. Taken together, our results implicated that exogenous H₂S could promote osteoclastogenesis by activating the PI3K/AKT/mTOR pathway to downregulate autophagy.

Objectives: Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level.Materials and methods: Bone structure and histological changes in Trpv6 knockout mice were examined using micro‐computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate‐resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC‐STAMP, Atp6v0d2 and TRAP, was measured by qRT‐PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF‐PI3K‐AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6.Results: We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF–PI3K–AKT signalling pathway. Blocking of the IGF–PI3K–AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation.Conclusions: Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.