Researchers identify protein that may help protect against osteoporosis

Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures.Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications.

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs).

New research published in The FASEB Journal indicates that increasing the expression of a particular gene may help to prevent bone loss associated with postmenopausal osteoporosis.

The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis.

For the study, investigators examined which genes are involved in turning precursor cells called bone marrow–derived mesenchymal stem cells (BMSCs) into cells that play a crucial role in bone formation. The screen identified a gene that encodes high mobility group AT-hook 1 (Hmga1), a protein that controls the expression of a variety of other genes.In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1)

In experiments conducted in rats, expression of Hmga1 increased during bone formation but decreased when rats’ ovaries were removed (mimicking menopause). Treating ovariectomized rats with extra Hmga1 partially reversed bone loss in the animals.

“Our study demonstrated that Hmga1 prevents bone loss by promoting the osteogenic differentiation of BMSCs in osteoporosis rats, suggesting that Hmga1 could be an important therapeutic target for osteoporosis,” said corresponding author Yihe Hu, PhD, of Zhejiang University, in China.

Reference:

Zhixin Wu, Jiayong Zhu, Yinxian Wen, Pengfei Lei, Jie Xie, Haifei Shi, Ronghuan Wu, Xianfeng Lou, Yihe Hu, Hmga1-overexpressing lentivirus protects against osteoporosis by activating the Wnt/β-catenin pathway in the osteogenic differentiation of BMSCs,

https://doi.org/10.1096/fj.202300488R