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. 2021 Oct;57(9):878-885.
doi: 10.1007/s11626-021-00632-z. Epub 2021 Nov 15.

1α,25-(OH)2-D3 promotes the autophagy during osteoclastogenesis by enhancing RANKL-RANK-TRAF6 signaling

Chengjian Yu  1 , Yunrong Zhu  2 , Xiaofei Lv  3 , Yabin Wang  4
Affiliations

1α,25-(OH)2-D3 promotes the autophagy during osteoclastogenesis by enhancing RANKL-RANK-TRAF6 signaling

Chengjian Yu et al. In Vitro Cell Dev Biol Anim. 2021 Oct.

Abstract

As the active form of vitamin D3, 1α,25-(OH)2-D3 promotes receptor activator for nuclear factor-κB ligand (RANKL)-induced autophagy in osteoclast precursors (OCPs). However, the relationship between 1α,25-(OH)2-D3 and RANKL signaling is still unknown. This study aimed to explore whether 1α,25-(OH)2-D3 regulates OCP autophagy and osteoclastogenesis through RANKL signaling. Our results showed that 1α,25-(OH)2-D3 directly decreased OCP autophagy while significantly enhancing the ability of RANKL to promote OCP autophagy. Moreover, 1α,25-(OH)2-D3 not only promoted the expression of key signaling proteins in OCPs induced by RANKL but also enhanced the coimmunoprecipitation levels of RANK and TRAF6. Notably, 1α,25-(OH)2-D3 significantly enhanced the autophagic activity and osteoclast differentiation of RANK-positive OCPs but did not affect the autophagic activity or osteoclast differentiation of RANK-negative OCPs. More importantly, 1α,25-(OH)2-D3 had no effect on autophagy or osteoclastogenesis in TRAF6-silenced OCPs. Overall, 1α,25-(OH)2-D3 could upregulate RANKL-RANK-TRAF6 signaling in OCPs, thereby promoting OCP autophagy and osteoclastogenesis.

Keywords: 1α,25-(OH)2-D3; Autophagy; Osteoclast; RANK; RANKL; TRAF6.

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