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Gu, Jianhong; Zhang, Xueqing; Zhang, Chuang; Li, Yawen; Bian, Jianchun; Liu, Xuezhong; Yuan, Yan; Zou, Hui; Tong, Xishuai; Liu, Zongping
International journal of molecular sciences, 12/2021, Letnik: 22, Številka: 24Journal Article
The active form of vitamin D, 1α,25-(OH)2D3, not only promotes intestinal calcium absorption, but also regulates the formation of osteoclasts (OCs) and their capacity for bone mineral dissolution. Gal-3 is a newly discovered bone metabolic regulator involved in the proliferation, differentiation, and apoptosis of various cells. However, the role of galectin-3 (gal-3) in OC formation and the regulatory effects of 1α,25-(OH)2D3 have yet to be explored. To confirm whether gal-3 contributes to the regulatory effects of 1α,25-(OH)2D3 on osteoclastogenesis, osteoclast precursors (OCPs) were induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). TRAP staining and bone resorption analyses were used to verify the formation and activation of OCs. qPCR, Western blotting, co-immunoprecipitation, and immunofluorescence assays were used to detect gene and protein expression. The regulatory effects of gal-3 in OC formation after treatment with 1α,25-(OH)2D3 were evaluated using gal-3 siRNA. The results showed that 1α,25-(OH)2D3 significantly increased gal-3 expression and inhibited OC formation and bone resorption. Expression levels of OC-related genes and proteins, matrix metalloproteinase 9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), and cathepsin K (Ctsk) were also inhibited by 1α,25-(OH)2D3. Gal-3 knockdown attenuated the inhibitory effects of 1α,25-(OH)2D3 on OC formation, activation, and gene and protein expression. In addition, gal-3 was co-localized with the vitamin D receptor (VDR). These data suggest that gal-3 contributes to the osteoclastogenesis inhibitory effect of lα,25-(OH)2D3, which is involved in bone and calcium homeostasis.
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