Journal
ORAL DISEASES
Volume 28, Issue 2, Pages 428-441Publisher
WILEY
DOI: 10.1111/odi.13745
Keywords
coupling factor; crosstalk; hypoxia; mandible; osteoclastogenesis; osteogenesis
Categories
Funding
- National Natural Science Foundation of China [81670961]
- Technology Committee Foundation of Shanghai [20Y11904000]
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HIF-1 alpha plays a key role in osteoclastogenesis and bone resorption during fracture healing, and influences bone healing through CT-1 secretion. These findings are important for understanding the pathogenesis of bone diseases.
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.
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