SM22α-lineage niche cells regulate intramembranous bone regeneration via PDGFRβ-triggered hydrogen sulfide production

• Published in: Cell reports (Cambridge) 2022-05, Vol.39 (5), p.110750-110750, Article 110750
• Main Authors: Zhou, Xueman, Liu, Jin, Zheng, Yingcheng, Zhang, Zhenzhen, Wu, Yange, Yang, Wenke, Liu, Jiaqi, Huang, Yanmei, Yi, Yating, Zhao, Zhihe, Xiao, Hengyi, Mo, Xianming, Wang, Jun
• Format: Article
• Language: English
• Subjects: Bone Regeneration; bone regeneration niche; CP: Cell biology; H2S; Hydrogen; hydrogen sulfide; Hydrogen Sulfide - pharmacology; Microfilament Proteins - metabolism; Muscle Proteins - metabolism; niche cell; Osteogenesis; PDGFRβ; platelet-derived growth factor receptors β; Receptor, Platelet-Derived Growth Factor beta - metabolism; SM22α
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110750

Bone stromal cells are critical for bone homeostasis and regeneration. Growing evidence suggests that non-stem bone niche cells support bone homeostasis and regeneration via paracrine mechanisms, which remain to be elucidated. Here, we show that physiologically quiescent SM22α-lineage stromal cells expand after bone injury to regulate diverse processes of intramembranous bone regeneration. The majority of SM22α-lineage cells neither act as stem cells in vivo nor show their expression patterns. Dysfunction of SM22α-lineage niche cells induced by loss of platelet-derived growth factor receptor β (PDGFRβ) impairs bone repair. We further show that PDGFRβ-triggered hydrogen sulfide (H2S) generation in SM22α-lineage niche cells facilitates osteogenesis and angiogenesis and suppresses overactive osteoclastogenesis. Collectively, these data demonstrate that non-stem SM22α-lineage niche cells support the niche for bone regeneration with a PDGFRβ/H2S-dependent regulatory mechanism. Our findings provide further insight into non-stem bone stromal niche cell populations and niche-regulation strategy for bone repair. [Display omitted] •Non-stem SM22α-lineage niche cells are activated by injury to drive bone regeneration•Loss of PDGFRβ induces dysfunction of SM22α-lineage cells and then impairs bone repair•PDGFRβ, but not PDGFRα, is required for H2S production of SM22α-lineage niche cells•PDGFRβ-driven H2S production by SM22α-lineage cells regulates stem and progenitor cell fate Zhou et al. identify the distinct function of SM22α-lineage stromal cells in regulating diverse processes of intramembranous bone regeneration. These niche cells are activated upon injury and modulate stem and progenitor cell fate with a unique PDGFRβ/H2S-dependent regulatory mechanism.