Submit a comment
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), an adipokine implicated in lipid metabolism, that influenced the fate of MSCs in BM during skeletal aging. Our studies revealed that ANGPTL8 steered MSCs toward adipogenic differentiation, overshadowing osteoblastogenesis. Mice with overexpressed ANGPTL8 exhibited reduced bone mass and increased BM adiposity, while those with transgenic depletion of ANGPTL8 showed lowered bone loss and less accumulation of BM fat. ANGPTL8 influenced the BM 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 an Angptl8 antisense oligonucleotide improved the phenotype of aging mice. Our research suggests that ANGPTL8 is a crucial regulator of senesence-related changes in the BM niche and the cell-fate switch of MSCs.
Authors
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
Guidelines
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.
- Comments appear on the Journal’s website and are linked from the original article’s web page.
- Authors are notified by email if their comments are posted.
- The Journal reserves the right to edit comments for length and clarity.
- No appeals will be considered.
- Comments are not indexed in PubMed.
Specific requirements
- Maximum length, 400 words
- Entered as plain text or HTML
- Author’s name and email address, to be posted with the comment
- Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
- Comments may not include figures
