2026 Volume 35 Issue 3 Pages 147-154
Mechanical stress (MS) loading induces alveolar bone remodeling by osteogenesis and osteoclastogenesis on the tension and compression sides, respectively during orthodontic tooth movement (OTM). Reduced blood flow alters low-oxygen conditions on the compression side of the MS loading force. Osteocytes constitute over 90% of bone cells and express receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), crucial for osteoclast differentiation, as well as sclerostin, which inhibits osteoblast differentiation, leading to reciprocal regulation in bone remodeling. However, many aspects of the relationship between mechanosensors expression in osteocytes and alveolar bone remodeling under hypoxia require clarification. Furthermore, osteogenesis-related molecule expression during OTM has focused on periodontal ligament cells, and their role in osteocytes remains unclear. We investigated mechanosensors expression in MLO-Y4 mouse osteocytes under hypoxia or CoCl2 treatment as pseudohypoxic condition and changes in the expression of osteogenesis-related molecules using the CCK-8 assay, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot. Compared with normoxia, hypoxia or CoCl2 treatment had little effect on the proliferation rate of MLO-Y4 cells. Hypoxia induced hypoxia-related molecule expression, including hypoxia-inducible factor 1α (HIF1α), decreased the RANKL/OPG ratio due to OPG upregulation, and downregulated sclerostin via phosphorylation of Akt and cyclic AMP response element-binding protein. In contrast, compression upregulated RANKL, increasing the RANKL/OPG ratio. MLO-Y4 cells expressed Piezo1 and activated Piezo1 upregulated HIF-1α expression. Our findings suggest that hypoxia enhances osteogenesis by downregulating the RANKL/OPG ratio and sclerostin expression, whereas compression enhances osteoclastogenesis by upregulating RANKL.
