김정하 (전남대학교 의과대학)

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전남대학교 의과대학

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Exp. Mol. Med., Sep 02 2024, | https://doi.org/10.1038/s12276-024-01302-2 Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts

Jung Ha Kim¹, Kabsun Kim¹, Inyoung Kim^1,2, Semun Seong^1,2, Jeong-Tae Koh^2,3 and Nacksung Kim^1,2

¹Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.

²Hard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea.

³Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea.

Corresponding author

Correspondence to Nacksung Kim.

Abstract

Stanniocalcin 1 (STC1) is a calcium- and phosphate-regulating hormone that is expressed in all tissues, including bone tissues, and is involved in calcium and phosphate homeostasis. Previously, STC1 expression was found to be increased by 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] administration in renal proximal tubular cells. In this study, we investigated whether STC1 directly regulates osteoblast differentiation or reciprocally controls the effects of 1,25(OH)₂D₃ on osteoblasts to contribute to bone homeostasis. We found that STC1 inhibited osteoblast differentiation in vitro and bone morphogenetic protein 2 (BMP2)-induced ectopic bone formation in vivo. Moreover, 1,25(OH)₂D₃ increased STC1 expression through direct binding to the Stc1 promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH)₂D₃-VDR signaling pathway through the upregulation of VDR expression mediated by the inhibition of Akt phosphorylation in osteoblasts. STC1 further increased the effects of 1,25(OH)₂D₃ on receptor activator of nuclear factor-κB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH)₂D₃. The long-bone phenotype of transgenic mice overexpressing STC1 specifically in osteoblasts was not significantly different from that of wild-type mice. However, compared with that in the wild-type mice, 1,25(OH)₂D₃ administration significantly decreased bone mass in the STC1 transgenic mice. Collectively, these results suggest that STC1 negatively regulates osteoblast differentiation and bone formation; however, the inhibitory effect of STC1 on osteoblasts is transient and can be reversed under normal conditions. Nevertheless, the synergistic effect of STC1 and 1,25(OH)₂D₃ through 1,25(OH)₂D₃ administration may reduce bone mass by inhibiting osteoblast differentiation.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-03)
연구진국내 연구진
분야 생명과학 > 분자생물학

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