The skeleton provides the scaffold to support body weight, enable body movement, control mineral homeostasis, and provide the location for hematopoiesis. Osteoclasts are specialized cells formed by the fusion of committed monocyte/macrophage hematopoietic lineage precursor cells. The importance of osteoclasts in bone homeostasis and health is evidenced by the diseases in which osteoclast formation and function are dysregulated, such as osteoporosis, fracture healing, osteoarthritis, and primary/metastatic bone cancer. All the time, osteoclasts, as “bone eaters”, are focused on exploring their role in bone homeostasis and diseases. With the development of single cell labeling and detection technologies and their wide application in the field of bone, the novel concept of osteoclast subtypes and their emerging functions have been continuously uncovered and improved. Cell-cell communication network coordinated by osteoclasts balances bone microenvironment, therefore, from the perspective of network, interpreting the relationship between osteoclasts and bone/joint diseases will help to understand the nature of the diseases better. Finally, we propose osteoclasts controlling-based strategies for rebuilding microenvironmental homeostasis, aiming to bone/cartilage disease intervention and regenerative repair.

In recent years, researchers have become focused on the relationship between lipids and bone metabolism balance. Moreover, many diseases related to lipid metabolism disorders, such as nonalcoholic fatty liver disease, atherosclerosis, obesity, and menopause, are associated with osteoporotic phenotypes. It has been clinically observed in humans that these lipid metabolism disorders promote changes in osteoporosis-related indicators bone mineral density and bone mass. Furthermore, similar osteoporotic phenotype changes were observed in high-fat and high-cholesterol-induced animal models. Abnormal lipid metabolism (such as increased oxidized lipids and elevated plasma cholesterol) affects bone microenvironment homeostasis via cross-organ communication, promoting differentiation of mesenchymal stem cells to adipocytes, and inhibiting commitment towards osteoblasts. Moreover, disturbances in lipid metabolism affect the bone metabolism balance by promoting the secretion of cytokines such as receptor activator of nuclear factor-kappa B ligand by osteoblasts and stimulating the differentiation of osteoclasts. Conclusively, this review addresses the possible link between lipid metabolism disorders and osteoporosis and elucidates the potential modulatory mechanisms and signaling pathways by which lipid metabolism affects bone metabolism balance. We also summarize the possible approaches and prospects of intervening lipid metabolism for osteoporosis treatment.

More than 50% of prostate cancer (PCa) patients have bone metastasis with osteoblastic lesions. MiR-18a-5p is associated with the development and metastasis of PCa, but it remains unclear whether it is involved in osteoblastic lesions. We first found that miR-18a-5p was highly expressed in the bone microenvironment of patients with PCa bone metastases. To address how miR-18a-5p affects PCa osteoblastic lesions, antagonizing miR-18a-5p in PCa cells or pre-osteoblasts inhibited osteoblast differentiation in vitro. Moreover, injection of PCa cells with miR-18a-5p inhibition improved bone biomechanical properties and bone mineral mass in vivo. Furthermore, miR-18a-5p was transferred to osteoblasts by exosomes derived from PCa cells and targeted the Hist1h2bc gene, resulting in Ctnnb1 up-regulation in the Wnt/β-catenin signaling pathway. Translationally, antagomir-18a-5p significantly improved bone biomechanical properties and alleviated sclerotic lesions from osteoblastic metastases in BALB/c nude mice. These data suggest that inhibition of exosome-delivered miR-18a-5p ameliorates PCa-induced osteoblastic lesions.