S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling

Xin,Jing; Wang,Zhaoxu; Shen,Yanju; Bai,Jing; Shen,Yafei

doi:10.3892/etm.2024.12538

S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling

Authors:
- Jing Xin
- Zhaoxu Wang
- Yanju Shen
- Jing Bai
- Yafei Shen
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Affiliations: Department of Endocrinology and Diabetes, Luohe Central Hospital, Luohe First People's Hospital, The First Affiliated Hospital of Luohe Medical College, Luohe, Henan 462000, P.R. China
Published online on: April 15, 2024 https://doi.org/10.3892/etm.2024.12538
Article Number: 250
Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteogenesis is a complex process of bone formation regulated by various factors, yet its underlying molecular mechanisms remain incompletely understood. The present study aimed to investigate the role of S100A16, a novel member of the S100 protein family, in the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) and uncover a novel Smad4‑mitogen‑activated protein kinase (MAPK)/Jun N‑terminal kinase (JNK) signaling axis. In the present study, the expression level of S100A16 in bone tissues and BMSCs from ovariectomized rats was evaluated and then the impact of S100A16 silencing on osteogenic differentiation was examined. Increased S100A16 expression was observed in bone tissues and BMSCs from ovariectomized rats, and S100A16 silencing promoted osteogenic differentiation. Further transcriptomic sequencing revealed that the Smad4 pathway was involved in S100A16 silencing‑induced osteogenesis. The results of western blot analysis revealed that S100A16 overexpression not only downregulated Smad4 but also activated MAPK/JNK signaling, which was validated by treatment with MAPK and JNK inhibitors U0126 and SP600125. Overall, in the present study, the novel regulatory factors influencing osteogenic differentiation were elucidated and mechanistic insights that could aid in the development of targeted therapeutic strategies for patients with osteoporosis were provided.

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