The dynamic transition of mature osteoblasts between active and quiescent states is crucial for maintaining bone homeostasis and is an important target in bone anabolic metabolism-related research. This study utilized spatially resolved osteoblast tracking transcriptomics technology, combined with lineage tracing and spatial sorting methods, to analyze the quiescent bone surface osteoblast state, identified TGF-β signaling as the core regulatory factor for osteoblast activation, and completed verification through multi-dimensional experiments. In a bone loss mouse model, the dual inhibition approach of TGF-β and sclerostin was found to be more effective in improving bone quality and alleviating bone loss compared to single inhibition of sclerostin. This discovery elucidated the molecular mechanism of TGF-β regulating the dynamics of osteoblasts and provided a dual-target strategy for the intervention of osteoporosis. This review addresses the regeneration and repair challenges caused by the heterogeneity of bone-cartilage tissue, with the tissue engineering system combining mesenchymal stem cells and biomaterial scaffolds as the core, clarifies the regulatory mechanism of biological physical signals on stem cell fate, systematically summarizes the progress in the design of biomimetic microenvironment scaffolds under mechanical biology guidance, and achieves precise regulation of mesenchymal stem cell lineage differentiation, providing theoretical support and design references for layered bone-cartilage regeneration, especially the regeneration of subchondral bone.

Original source:
1. Journal of Publication: Bone Research
2. Publication date: April 4, 2026
3. DOI: 10.1038/s41413-026-00521-9
4. Authors: Ahyoun Choi, Ji Yeon Lee, 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