SM22α-lineage niche cells regulate intramembranous bone regeneration via PDGFRβ-triggered hydrogen sulfide production
Xueman Zhou,
Jin Liu,
Yingcheng Zheng,
Zhenzhen Zhang,
Yange Wu,
Wenke Yang,
Jiaqi Liu,
Yanmei Huang,
Yating Yi,
Zhihe Zhao,
Hengyi Xiao,
Xianming Mo,
Jun Wang
Affiliations
Xueman Zhou
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Aging Research, State Key Laboratory of Biotherapy & National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Jin Liu
Laboratory of Aging Research, State Key Laboratory of Biotherapy & National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Corresponding author
Yingcheng Zheng
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Aging Research, State Key Laboratory of Biotherapy & National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Zhenzhen Zhang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Aging Research, State Key Laboratory of Biotherapy & National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Yange Wu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Wenke Yang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Jiaqi Liu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Yanmei Huang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Yating Yi
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Zhihe Zhao
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
Hengyi Xiao
Laboratory of Aging Research, State Key Laboratory of Biotherapy & National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Xianming Mo
Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Corresponding author
Jun Wang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Corresponding author
Summary: 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.
