Bone metabolic disorders include osteolysis, osteoporosis, osteoarthritis and rheumatoid arthritis. Osteoblasts and osteoclasts are two major types of cells in bone constituting homeostasis. The imbalance between bone formation by osteoblasts and bone resorption by osteoclasts has been shown to have a direct contribution to the onset of these diseases. Recent evidence indicates that autophagy and mitophagy, the selective autophagy of mitochondria, may play a vital role in regulating the proliferation, differentiation and function of osteoblasts and osteoclasts. Several signaling pathways, including PINK1/Parkin, SIRT1, MAPK8/FOXO3, Beclin-1/BECN1, p62/SQSTM1, and mTOR pathways, have been implied in the regulation of autophagy and mitophagy in these cells. Here we review the current progress about the regulation of autophagy and mitophagy in osteoblasts and osteoclasts in these bone metabolic disorders, as well as the molecular signaling activated or deactivated during this process. Together, we hope to draw attention to the role of autophagy and mitophagy in bone metabolic disorders, and their potential as a new target for the treatment of bone metabolic diseases and the requirements of further mechanism studies.
Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of prosthesis loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic prosthesis loosening.
Articular cartilage defects have been addressed by using multiple strategies. In the last two decades, promising new strategies by using assorted scaffolds and cell sources to induce tissue regeneration have emerged, such as autologous chondrocyte implantation (ACI) and mesenchymal stem cell implantation (MSCI). However, it is still controversial in the clinical strategies when to choose these treatments. Thus, we conducted a systematic review and meta-analyses to compare the efficacy and safety of different cartilage treatments. In our study, 17 studies were selected to compare different treatments for cartilage defects. The results of meta-analyses indicated that cell-based cartilage treatments showed significant better efficacy than cell-free treatments did (OR: 4.27, 95% CI: 2.19–8.34; WMD: 10.11, 95% CI: 2.69–16.53). Another result indicated that MACT had significant better efficacy than traditional ACI did (OR: 0.49, 95% CI: 0.30–0.82). Besides, the incidence of graft hypertrophy of MACT was slightly lower than that of traditional ACI (OR: 2.43, 95% CI: 1.00–5.94). Current data showed that the cell-based treatments and MACT are better options for cartilage treatments, but more well-designed comparative studies are still needed to enhance our understanding of different treatments for cartilage defects.
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