HIF-1α regulates osteoclast activation and mediates osteogenesis during mandibular bone repair via CT-1

Objectives Hypoxia is one of the characteristics of microenvironmental changes after orthognathic surgery for fractures. HIF-1 alpha is a main regulator of the hypoxic response and plays a crucial role in bone formation, remodelling, and homeostasis. Osteoclasts participate in bone absorption and affect osteogenesis, and osteoclasts differentiate in a path from the oxygen-rich bone marrow to oxygen-deficient bone lesions. Thus, we aimed to study the key functions of HIF-1 alpha in osteoclasts during mandibular healing after osteotomy. Materials and Methods The function of HIF-1 alpha in osteoclasts during fracture healing in osteoclast-specific HIF-1 alpha-conditional-knockout mice was investigated in mandibular osteotomy. Primary osteoclasts were used to explore the expression of HIF-1 alpha and cardiotrophin-1 (CT-1) at both the mRNA and protein levels. The ability of BMSCs co-cultured with conditioned media from osteoclast-specific HIF-1 alpha-knockout primary osteoclasts was detected using osteoclast-mediated osteogenesis experiments. Results Hypoxia-inducible factor-1 alpha increased osteoclastogenesis and bone resorption, and a delay in bone healing was found in osteoclast-specific HIF-1 alpha-conditional-knockout mice compared with normal mice. HIF-1 alpha-knockout primary osteoclasts inhibited bone resorption and CT-1 expression, and HIF-1 alpha enhanced the osteoclast-mediated stimulation of BMSC differentiation by secreting CT-1. Conclusions Hypoxia-inducible factor-1 alpha can play a key role in the physiology and pathogenesis of bone resorption by promoting osteoclastogenesis during fracture and influencing osteogenesis through CT-1 during bone healing.