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Osteoporosis and osteoarthritis are common diseases in an aging society, are considered metabolic diseases, and affect the quality of life of older adults. In addition, the gut microbiome is considered an additional organ to regulate bone metabolism. In the past decade, people have been studying the relationship between gut microbiota and bone metabolism. The role and mechanism of the gut microbiota in regulating bone metabolism is very important to improve the development of osteoporosis and osteoarthritis. Depletion of the gut microbiota as a method of studying the role of the gut microbiota was provided strategies to enhance the role of the gut microbiota in regulating osteoporosis and osteoarthritis. In this review, we discuss how depletion of the gut microbiota affects osteoporosis and osteoarthritis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guan, Luo, Liu, Guan, Zhang, Li and Tao.)

Gut microbiota dysbiosis has been studied under the pathological conditions of osteoarthritis (OA). However, the effect of antibiotic-induced gut flora dysbiosis on OA remains incompletely understood at present. Herein, we used a mouse (8 weeks) OA model of destabilization of the medial meniscus (DMM) and gut microbiome dysbiosis induced by antibiotic treatment with ampicillin and neomycin for 8 weeks. The results show that antibiotic-induced intestinal microbiota dysbiosis reduced the serum level of lipopolysaccharide (LPS) and the inflammatory response, such as suppression of the levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can lead to decreased matrix metalloprotease-13 (MMP-13) expression and improvement of OA after joint injury. In addition, trabecular thickness (Tb.Th) and osteophyte scores were increased significantly in antibiotic-induced male mice compared with female mice. We further used network correlation analysis to verify the effect of gut microbiota dysbiosis on OA. Therefore, the present study contributes to our understanding of the gut-joint axis in OA and reveals the relationship between the inflammatory response, sex and gut microbiota, which may provide new strategies to prevent the symptoms and long-term sequelae of OA. Conclusion: Our data showed that gut microbiome dysbiosis alleviates the progression of OA., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Ferroptosis is an iron‐dependent cell death that has been found to aggravate the progression of osteoarthritis (OA) and gut microbiota‐ OA axis refers to the bidirectional information network between the gut microbiota and OA, which may provide a new way to protect the OA. However, the role of gut microbiota‐derived metabolites in ferroptosis‐relative osteoarthritis remains unclear. The objective of this study was to analyze the protective effect of gut microbiota and its metabolite capsiate (CAT) on ferroptosis‐relative osteoarthritis in vivo and in vitro experiments. From June 2021 to February 2022, 78 patients were evaluated retrospectively and divided into two groups: The health group (n = 39) and the OA group (n = 40). Iron and oxidative stress indicators were determined in peripheral blood samples. And then in vivo and in vitro experiments, a surgically destabilized medial meniscus (DMM) mice model was established and treated with CAT or Ferric Inhibitor‐1 (Fer‐1). Solute Carrier Family 2 Member 1 (SLC2A1) short hairpin RNA (shRNA) was utilized to inhibit SLC2A1 expression. Serum iron was increased significantly but total iron binding capacity was decreased significantly in OA patients than healthy people (p < 0.0001). The least absolute shrinkage and selection operator clinical prediction model suggested that serum iron, total iron binding capacity, transferrin, and superoxide dismutase were all independent predictors of OA (p < 0.001). Bioinformatics results suggested that SLC2A1, Metastasis‐Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and HIF‐1α (Hypoxia Inducible Factor 1 Alpha)‐related oxidative stress signaling pathways play an important role in iron homeostasis and OA. In addition, gut microbiota 16s RNA sequencing and untargeted metabolomics were used to find that gut microbiota metabolites CAT in mice with osteoarthritis were negatively correlated with Osteoarthritis Research Society International (OARSI) scores for chondrogenic degeneration (p = 0.0017). Moreover, CAT reduced ferroptosis‐dependent osteoarthritis in vivo and in vitro. However, the protective effect of CAT against ferroptosis‐dependent osteoarthritis could be eliminated by silencing SLC2A1. SLC2A1 was upregulated but reduced the SLC2A1 and HIF‐1α levels in the DMM group. HIF‐1α, MALAT1, and apoptosis levels were increased after SLC2A1 knockout in chondrocyte cells (p = 0.0017). Finally, downregulation of SLC2A1 expression by Adeno‐associated Virus (AAV) ‐SLC2A1 shRNA improves osteoarthritis in vivo. Our findings indicated that CAT inhibited HIF‐1a expression and reduced ferroptosis‐relative osteoarthritis progression by activating SLC2A1. [ABSTRACT FROM AUTHOR]