| First Author | Choi A | Year | 2026 |
| Journal | Bone Res | Volume | 14 |
| Issue | 1 | PubMed ID | 41927532 |
| Mgi Jnum | J:392473 | Mgi Id | MGI:8434412 |
| Doi | 10.1038/s41413-026-00521-9 | Citation | Choi A, et al. (2026) Spatially resolved osteoblast-traced transcriptomics uncovers TGF-beta as a combination target with sclerostin in osteoporosis. Bone Res 14(1) |
| abstractText | 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-beta) 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-beta and sclerostin enhanced bone mass and mitigated bone loss more effectively than sclerostin inhibition alone. These findings reveal a mechanistic role for TGF-beta in regulating osteoblast dynamics and propose a dual-target therapeutic strategy that enhances the efficacy of anti-sclerostin treatment in osteoporosis. |
