Mandibular osteotomy‐induced hypoxia enhances osteoclast activation and acid secretion by increasing glycolysis. Issue 7 (12th December 2018)

• Record Type: Journal Article
• Authors: Tang, Yi; Zhu, Jie; Huang, Danqing; Hu, Xiu; Cai, Yun; Song, Xiwen; Song, Zhaohui; Hong, Chaoyue; Feng, Zifan; Kang, Feiwu
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 7(2019:Jul.)
• Page Start: 11165
• Page End: 11175
• Publication Date: 2018-12-12
• Subjects: bone resorption -- glycolysis -- HIF‐1α -- mandibular osteotomy -- osteoclast; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27765
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: The rapid bone remodeling after osteotomy has been reported for a long time. However, the underlying mechanism promoting the active bone reconstruction was still to be elucidated. Since not only the bone, blood vessels, and supportive tissues, but also the local microenvironment were destroyed, if the changes on the cell metabolism was contributed to the accelerated bone remodeling came into sight. In present study, we found that the mandibular osteotomy in rabbit activated osteoclasts, as well as the expression of hypoxia‐inducible factor 1α (HIF‐1α) in alveolar bone. Hypoxia or HIF‐1α could enhanced osteoclastogenesis, bone absorption, and lactic acid concentration in receptor activator of nuclear factor κΒ ligand‐induced RAW264.7 cells. Coincided with the upregulated HIF‐1α expression, HIF‐driven glycolytic enzymes, such as lactate dehydrogenase A (LDHA), glucokinase (GCK), pyruvate kinase M2 (PKM2), and phosphofructokinase1 (PFK1), were found massively increased in both hypoxic RAW264.7 cells and the alveolar HIF‐1α‐positive osteoclasts after mandibular osteotomy. Knockdown of HIF‐1α suppressed not only the hypoxia‐mediated glycolysis, but also the hypoxia‐induced acid secretion and bone resorption in RAW264.7 cells. Application of inhibitor on glycolysis gave rise to the similar results as HIF‐1α knockdown. Our findings suggested that hypoxia‐driven glycolysis in osteoclasts was an adaptive mechanism to permit alveolar bone remodeling after mandibular osteotomy. Abstract : The rapid bone remodeling after osteotomy has been reported for a long time. However, the underlying mechanism promoting the active bone reconstruction was still to be elucidated. Hypoxia‐driven glycolysis in osteoclasts was an adaptive mechanism to permit alveolar bone remodeling after mandibular osteotomy.