ECTS Abstracts (2015) 1 P200

Distinct roles of HIF-1[alpha] and HIF-2[alpha] in osteoblast and osteoclast function

Jeong-Tae Koh, Min-Suk Kook & Je-Hwang Ryu

Chonnam National University, Gwangju, Republic of Korea.

Although the possible roles of hypoxia have been demonstrated extensively, much less is known about the regulatory mechanisms of HIF (hypoxia-inducible factor) families on osteoporosis. We undertook this study to explore the distinct roles of HIF-1α and HIF-2α in the regulation of bone mass. The role of HIF-1α and HIF-2α was investigated by overexpression or knockdown analysis. Both HIF-1α and HIF-2α significantly increased Rankl expression during osteoblast differentiation. In addition, RANKL-induced osteoclast differentiation was clearly regulated by HIF-2α (not by HIF-1α). We found that this regulation was mediated by regulation of osteoclast fusion-related genes such as DC-stamp and OC-stamp. We further examined the in vivo role of HIF-1α and HIF-2α in linking osteoblast and osteoclast functions on osteoporosis in ovariectomised-knockout mice lacking HIF-1α or HIF-2α. HIF-1α or HIF-2α deficiency in mice reduced the development of ovariectomy-induced bone loss compared with their wild type mice. Collectively, these results indicate that HIF-1α and HIF-2α have a pivotal role in the regulation of bone mass through distinct mechanisms.

Disclosure: The authors declared no competing interests.

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