Journal Article

Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 cooperatively regulate bone mineralization by osteoblasts

Seong, Semun, Kim, Jung Ha, Koh, Jeong-Tae, Kim, Kabsun, Kim, Nacksung, Kim, Inyoung

2024

Overview

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 D 3 [1,25(OH) 2 D 3 ] 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) 2 D 3 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) 2 D 3 increased STC1 expression through direct binding to the Stc1 promoter of the vitamin D receptor (VDR). STC1 activated the 1,25(OH) 2 D 3 –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) 2 D 3 on receptor activator of nuclear factor-κB ligand (RANKL) secretion and inhibited osteoblast differentiation by exhibiting a positive correlation with 1,25(OH) 2 D 3 . 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) 2 D 3 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) 2 D 3 through 1,25(OH) 2 D 3 administration may reduce bone mass by inhibiting osteoblast differentiation. Bone mineralization regulation: Stanniocalcin 1 & Vitamin D3 synergize In the field of bone health, it’s important to understand how our bodies control bone creation. This research investigates how Stanniocalcin 1 and 1,25-dihydroxyvitamin D3 work together to affect bone mineralization by osteoblasts. The team used mouse models and cell cultures in their experiment. They found that STC1 alone can slow down osteoblast differentiation and bone creation, but this effect is stronger when 1,25-dihydroxyvitamin D3 is also present. This suggests a complex relationship that could affect bone health. They conclude that the combined regulation by STC1 and 1,25-dihydroxyvitamin D3 is a key factor in bone mineralization, providing new insights into managing bone health. This knowledge could lead to treatments for bone diseases by targeting these pathways. Future research may show how to adjust these interactions for treatment benefits, potentially improving results for those with bone health problems. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group,생화학분자생물학회
• Subject: 38/1 / 38/109 / 38/77 / 42/44 / 631/337/572 / 631/80/86/2363 / 64/60 / 82/1 / 96/95 / AKT protein / Animal models / Artificial intelligence / Biomedical and Life Sciences / Biomedicine / Bone diseases / Bone growth / Bone mass / Bone morphogenetic protein 2 / Bone turnover / Calcitriol / Calcium homeostasis / Calcium phosphates / Cell culture / Cell differentiation / Homeostasis / Long bone / Medical Biochemistry / Mineralization / Molecular Medicine / Osteoblastogenesis / Osteoblasts / Osteogenesis / Phenotypes / Phosphorylation / Signal transduction / Stem Cells / Synergism / Transgenic animals / Transgenic mice / Vitamin D3 / 생화학