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Spatially resolved osteoblast-traced transcriptomics uncovers TGF-βas a combination target with sclerostin in osteoporosis 认领 引用
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作者 Ahyoun Choi Ji Yeon Lee +14 位作者 Hyejin Yoon Xiangguo Che Minkyeong Choi Yongkuk Park Kyoungseob Shin Hyunho Lee Jimin Park Sung Hye Kong Jinhyun Kim Amos Chungwon Lee Chan Soo Shin Je-Yong Choi Jungwoo Lee Sunghoon Kwon Sang Wan Kim 《Bone Research》 SCIE CAS CSCD 2026年第2期640-652,共13页
Dynamic transitions of mature osteoblasts between active and quiescent states are essential for bone homeostasis and present a promising target for osteoanabolic therapy.However,these transitions remain poorly underst... Dynamic transitions of mature osteoblasts between active and quiescent states are essential for bone homeostasis and present a promising target for osteoanabolic therapy.However,these transitions remain poorly understood due to cellular heterogeneity and limited spatial context.Here,we employed spatially resolved osteoblast-traced transcriptomics,integrating an osteoblast-specific lineage tracing study and spatially resolved laser-activated cell sorting(SLACS),to profile osteoblast states on quiescent bone surfaces.This approach identified transforming growth factor-beta(TGF-β)signaling as a regulator of osteoblast activation.We further validated this role using single-cell RNA sequencing,in vitro functional assays,and in vivo.In a hindlimb unloading mouse model,dual inhibition of TGF-βand sclerostin enhanced bone mass and mitigated bone loss more effectively than sclerostin inhibition alone.These findings reveal a mechanistic role for TGF-βin regulating osteoblast dynamics and propose a dual-target therapeutic strategy that enhances the efficacy of anti-sclerostin treatment in osteoporosis. 展开更多
关键词 osteoanabolic therapyhoweverthese profile osteoblast states sclerostin spatially resolved osteoblast traced transcriptomics transforming growth factor beta bone homeostasis cellular heterogeneity osteoblast activation
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