The role of physical forces in osteoclastogenesis

The movements of life at every level from organs, tissues, cells to sub‐cells, are all conducted in certain physical environments. In the human body, skeletal tissue among all connective tissues is influenced the most by physical forces. Studying the biological behavior of bone cells under different physical environments is helpful in further understanding bone homeostasis and metabolism. Among all bone cells, osteoclast (OC) and OC steered bone remodeling is one of the key points in bone metabolism. In the past few decades, people's understanding of OC was mostly limited to its involvement of bone resorption under physiological and pathological conditions. However, more and more studies started to focus on how physical forces affect the formation and differentiation of OC. This review tries to illustrate the knowledge up to date about how osteoclastogenesis is regulated by physical forces through direct and indirect ways, including fluid shear force, compressive force, and microgravity. The direct way describes the straightforward effects produced by different forces in osteoclastogenesis, whereas the indirect way describes the effects of different forces in osteoclastogenesis through regulation of other bone cells when a certain force is applied. Molecular mechanisms were analyzed and reviewed in both direct and indirect regulation by different forces. Finally, we discussed the status quo and tendency of related research, as well as other unresolved issues, and some future prospects.