This paper is aimed to investigate the effect of rest-inserted loading on the mechanosensitivity of osteocytes. In the investigation, cultured MLO-Y4 osteocyte-like cells were strained on cyclic compressive force (CCF) by the self-made compressive loading device. Then we observed the effect of different rest periods-inserted loading (5 s, 15 s, 30 s, respectively) on the mechanosensitivity of osteocytes. We then determined the levels of secreted nitric oxide (NO) and prostaglandin E2 (PGE2) by Griess method and enzyme linked immunosorbent assay (ELISA), respectively. We then stained the cytoskeleton F-actin using immunofluorescence. We found that the expressions of NO and PGE2 in rest-inserted strained groups (>15 s) were significantly increased compared to those in the continuous strained group. And rest-inserted loading promoted the parallel alignment of stress fibers. It indicates that rest-inserted loading could promote the mechanosensitivity of osteocytes, and this might be related to the parallel alignment of stress fibers.
Bone remodeling requires an intimate cross-talk between osteoclasts and osteoblasts and is tightly coordinated with regulatory proteins that interact through complex autocrine/paracrine processes. Osteocytes, bone lining cells, osteomacs and vascular endothelial cells also regulate bone remodeling in the basic multicellular unit (BMU) via cell signaling networks of ligand-receptor complexes. In addition, through secreted and membrane-bound factors in the bone microenvironment, T and B lymphocytes mediate bone homeostasis for osteoimmunology. Osteoporosis and other bone diseases occur because multicellular communication within the BMU is disrupted. This review focuses on the roles of the cells in the BMU and the interaction between these cells and the factors involved in regulating bone remodeling at the cellular level. Understanding the process of bone remodeling and related genes could help us to lay the foundation for drug development against bone diseases.
Objective To review the research progress of exosomes (EXOs) derived from different cells in the treatment of osteoporosis (OP). Methods Recent relevant literature about EXOs for OP therapy was extensively reviewed. And the related mechanism and clinical application prospect of EXOs derived from different cells in OP therapy were summarized and analyzed. Results EXOs derived from various cells, including bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, osteocytes, and endothelial cells, et al, can participate in many links in the process of bone remodeling, and their mechanisms involve the regulation of proliferation and differentiation of bone-related cells, the promotion of vascular regeneration and immune regulation, and the suppression of inflammatory reactions. A variety of bioactive substances contained in EXOs are the basis of regulating the process of bone remodeling, and the combination of genetic engineering technology and EXOs-based drug delivery can further improve the therapeutic effect of OP. Conclusion EXOs derived from different cells have great therapeutic effects on OP, and have the advantages of low immunogenicity, high stability, strong targeting ability, and easy storage. EXOs has broad clinical application prospects and is expected to become a new strategy for OP treatment.