ALG5 Downregulation Inhibits Osteogenesis and Promotes Adipogenesis by Regulating the N-glycosylation of SLC6A9 in Osteoporosis

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2025 Jan 6

PMID 39760914

Authors

Quanfeng Li

Wenjie Liu

Yunhui Zhang

Jiahao Jin

Pengfei Ji

Zihao Yuan

Yibin Zhang

Pei Feng

Yanfeng Wu

Huiyong Shen

Peng Wang

Affiliations

Soon will be listed here.

Abstract

Osteoporosis is characterized by decreased bone mass and accumulation of adipocytes in the bone marrow. The mechanism underlying the imbalance between osteoblastogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) remains unclear. We found that ALG5 was significantly downregulated in BMSCs from osteoporotic specimens. ALG5 knockdown inhibited osteogenic differentiation and increased adipogenic differentiation of BMSCs. ALG5 deficiency diminished the N-glycosylation of SLC6A9, thereby altering its protein stability and disrupting SLC6A9-mediated glycine uptake in BMSCs. ALG5 overexpression by adeno-associated virus serotype 9 (rAAV9) alleviated bone loss in OVX mice. Taken together, our findings suggest a novel role for the ALG5-SLC6A9-glycine axis in the imbalance of BMSC differentiation in osteoporosis. Moreover, we identify ALG5 overexpression as a potential therapeutic strategy for treating osteoporosis.

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