Angiopoietin-like 8 governs osteoblast-adipocyte lineage commitment during skeletal aging.

Yaming Guo, Zeqing Zhang, Junyu He, Peiqiong Luo, Zhihan Wang, Yurong Zhu, Xiaoyu Meng, Limeng Pan, Ranran Kan, Yuxi Xiang, Beibei Mao, Yi He, Siyi Wang, Yan Yang, Fengjing Guo, Hongbo You, Feng Li, Danpei Li, Yong Chen, Xuefeng Yu

Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · pubmed

Paper

Abstract

A distinguishing feature of older mesenchymal stem cells (MSCs) from bone marrow (BM) is the transition in their differentiation capabilities from osteoblasts to adipocytes. However, the mechanisms underlying these cellular events during the aging process remain unclear. We identified Angiopoietin-like protein 8 (ANGPTL8), a newly found adipokine implicated in lipid metabolism, that influences the fate of MSCs in BM during skeletal aging. Our studies revealed that ANGPTL8 steered MSCs towards adipogenic differentiation, overshadowing osteoblastogenesis. Mice with overexpressed ANGPTL8 exhibited reduced bone mass and increased bone marrow adiposity, while those with transgenic depletion of ANGPTL8 showed lowered bone loss and less accumulation of bone marrow fat. ANGPTL8 influenced the bone marrow niche of MSCs by inhibiting the Wnt/β-catenin signaling pathway. Partial inhibition of PPARγ rescued some aspects of the phenotype in MSCs with ANGPTL8 overexpression. Furthermore, treatment with Angptl8-Antisense Oligonucleotide (Angptl8-ASO) improved the phenotype of aging mice. The research proposes that ANGPTL8 is a critical regulator of senesence-related changes in the BM niche and the cell fate switch of MSCs.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

ANGPTL8 influences the differentiation of mesenchymal stem cells towards adipocytes, impacting skeletal aging. The paper addresses a mechanism related to the aging process and the cellular changes that occur in mesenchymal stem cells, which are relevant to understanding and potentially mitigating age-related decline in bone health.

Author of this paper? Send a correction.