Break and then stand: novel insight into osteoclast functions in the skeletal system

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.