Enhancement of tenogenic differentiation of rat tendon‐derived stem cells by biglycan

Abstract

Biglycan (BGN) has been identified as one of the critical components of the tendon‐derived stem cells (TDSCs) niche and may be related to tendon formation. However, so far, no study has demonstrated whether the soluble BGN could induce the tenogenic differentiation of TDSCs in vitro. The aim of this study was to investigate the effect of BGN on the tenogenic differentiation of TDSCs. The proliferation and tenogenic differentiation of TDSCs exposed to different concentrations of BGN (0, 50, 100, and 500 ng/ml) were determined by the live/dead cell staining assay, CCK‐8 assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot analysis. The BGN signaling pathway of TDSCs (with and without 50 ng/ml of BGN) was determined by western blot analysis and qRT‐PCR analysis. At a concentration of 50 ng/ml, BGN increased the expression of the tenogenic markers THBS‐4 and TNMD at both the messenger RNA (mRNA) and protein levels. Meanwhile, 50 ng/ml of BGN inhibited the expression of the chondrogenic and osteogenic markers SOX9, ACN, and RUNX2 at both the mRNA and protein levels. Moreover, BGN (50 ng/ml) affected the expression of the components of the extracellular matrix of TDSCs. Additionally, BGN activated the Smad1/5/8 pathway as indicated by an increase in phosphorylation and demonstrated by inhibition experiments. Upregulation in the gene expression of BMP‐associated receptors (BMPRII, ActR‐IIa, and BMPR‐Ib) and Smad pathway components (Smad4 and 8) was observed. Taken together, BGN regulates tenogenic differentiation of TDSCs via BMP7/Smad1/5/8 pathway and this regulation may provide a basic insight into treating tendon injury.

The “other” 15–40%: The Role of Non‐Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon

“…Biglycan expression was increased after tendon injury, in contrast to decorin, which was decreased . Moreover, biglycan contributes to the tendon stem/progenitor cell (TSPC) niche, where biglycan induced tenogenic differentiation of TSPCs while simultaneously inhibiting the chondrogenic and osteogenic differentiation program …”

“…Despite these challenges, decellularized tendon tissue allografts have been evaluated in small and large animal models and showed some promise in augmenting tendon repair after injury . In addition, overexpression or exogenous addition of individual ECM proteins in combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy . An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

“…72,73 Moreover, biglycan contributes to the tendon stem/progenitor cell (TSPC) niche, where biglycan induced tenogenic differentiation of TSPCs while simultaneously inhibiting the chondrogenic and osteogenic differentiation program. 6,74 Lumican Lumican interacts with collagen type I and regulates collagen fibril assembly. 75 Addition of purified lumican to cells limits collagen fibril growth in vitro, resulting in thinner fibrils.…”

“…173 OTHER ECM PROTEINS IN TENDON combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy. 74,[180][181][182] An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

Hierarchically Demineralized Cortical Bone Combined With Stem Cell–Derived Extracellular Matrix for Regeneration of the Tendon-Bone Interface

“…In general, our results and previous studies demonstrated that SDF-1 from ECM could recruit endogenous stromal cells, and biglycan from ECM could further induce multidirectional differentiation of recruited stromal cells to promote healing of the tendon-bone interface. 66,68 Although the hDCB group had more new formation of bone and fibrocartilage than the DCB group, there was no significant difference in the results of micro-CT and biomechanical testing between the 2 groups. However, hDCB-ECM significantly improved the ultimate tensile stress and Young modulus of the tendon-bone interface compared with DCB.…”