Tissue-specific extracellular matrix (ECM) proteins can play a key role in regulating the fate of stem cells and can potentially be utilized for therapeutic applications. Realising this potential requires further characterization of the diversity of biomolecules present in tissue-specific ECMs and an evaluation of their role as regulatory cues for regenerative medicine applications. The goal of this study was to identify specific soluble factors within the ECM of articular cartilage (AC) and growth plate (GP) that may impart chondro-inductivity or osteo-inductivity respectively. To this end, the significantly different proteins between both matrisomes were searched against the STRING database platform, from which C-type lectin domain family-11 member-A (CLEC11A) and S100 calcium-binding protein-A10 (S100A10) were identified as potential candidates for supporting osteogenesis, and Gremlin-1 (GREM1) and TGF-β induced gene human clone-3 (βIGH3) were identified as potential candidates for supporting stable chondrogenesis. Stimulation of chondrogenically-primed bone marrow-derived stem cells (BMSCs) with the AC-specific proteins GREM1 and βIGH3 had no noticeable effect on the deposition of collagen-II, a marker of chondrogenesis, but appeared to suppress the production of the hypertrophic marker collagen-X, particularly for higher concentrations of GREM1. Stimulation with GREM1 was also found to suppress the direct osteoblastic differentiation of BMSCs. In contrast, stimulation with the GP-specific factors CLEC11A and S100A10 was found to enhance osteogenesis of BMSCs, increasing the levels of mineralization, particularly for higher concentration of CLEC11A. Together these results demonstrate that AC- and GP-specific proteins may play a key role in developing novel strategies for engineering phenotypically stable articular cartilage or enhancing the regeneration of critically-sized bone defects.

组织特异性细胞外基质（ECM）蛋白可在调节干细胞的命运中发挥关键作用，并有可能用于治疗应用。要实现这一潜力，就需要进一步表征组织特异性ECM中存在的生物分子的多样性，并评估其作为再生医学应用的调控线索的作用。这项研究的目的是确定在关节软骨（AC）和生长板（GP）的ECM中可能分别赋予软骨诱导性或骨诱导性的特定可溶性因子。为此，我们在STRING数据库平台上搜索了两种基质之间显着不同的蛋白质，从中确定C型凝集素结构域家族11成员A（CLEC11A）和S100钙结合蛋白A10（S100A10）是支持成骨的潜在候选对象，而Gremlin-1（GREM1）和TGF-β诱导的基因人类克隆3（βIGH3）被确定为支持稳定软骨形成的潜在候选者。用AC特异性蛋白GREM1和βIGH3刺激软骨源性骨髓衍生干细胞（BMSC）对软骨形成标记胶原II的沉积没有明显影响，但似乎抑制了肥大标记的产生胶原蛋白X，特别是对于较高浓度的GREM1。还发现用GREM1刺激可抑制BMSC的直接成骨细胞分化。相反，发现使用GP特异性因子CLEC11A和S100A10刺激可增强BMSC的成骨作用，增加矿化水平，尤其是对于浓度较高的CLEC11A。这些结果共同表明，AC和GP特异性蛋白可能在开发新的策略以工程化表型稳定的关节软骨或增强临界大小的骨缺损的再生中起关键作用。