Based on the skeletal-muscle dual stem cell chemotaxis and bidirectional differentiation mechanism to reinterpret the “sinew-bone interdependence” theory

The “sinew-bone interdependence” theory is a core paradigm in traditional Chinese medicine (TCM) orthopedics and traumatology. Rooted in the visceral manifestation doctrine of “the liver governing sinews and the kidney governing bones,” this theory emphasizes the structural dependency, functional synergy, and pathological inter-transmission between sinews and bones. However, traditional interpretive pathways have largely remained at the level of descriptive deduction concerning anatomy, visceral manifestations, and biomechanics, failing to elucidate the cellular executors and molecular mechanisms underpinning the sinew-bone association. In this theoretical article, we propose a hypothesis that intercellular communication between skeletal muscle satellite cells (MuSCs) and bone marrow mesenchymal stem cells (BMSCs) may provide a cellular-molecular basis for this classical theory. This article systematically reviews the molecular identity of MuSCs and BMSCs, the molecular basis of stem cell chemotaxis centered on the SDF-1/CXCR4 axis, and the existing evidence for the bidirectional chemotaxis of these two stem cell types. It further analyzes the network characteristics of the Wnt/β-catenin, BMP/Smad, and Notch signaling pathways in regulating lineage specification and the research progress on multi-target interventions by Chinese herbal medicines. Building on this foundation, we propose a testable hypothesis of “sinew injury recruiting bone, bone damage summoning muscle” and construct a “Dual Stem Cell-Chemotaxis-Differentiation” (DSCD) model. We emphasize that this model represents a theoretical framework requiring experimental validation rather than an established mechanism. This model redefines the sinew-bone system as a dynamic cellular niche maintained by a chemotactic axis, an exosome-based communication network, and a convergence of multiple signaling pathways. This article aims to propose measurable molecular connotations for classical theory, thereby stimulating further experimental investigation in TCM orthopedics in the era of regenerative medicine.