BMP-2 stimulated non-tenogenic differentiation and promoted proteoglycan deposition of tendon-derived stem cells (TDSCs) in vitro

J Orthop Res. 2013 May;31(5):746-53. doi: 10.1002/jor.22290. Epub 2012 Dec 13.

Abstract

We hypothesized that BMP-2 might induce non-tenocyte differentiation and increase production of proteoglycans of tendon-derived stem cells (TDSCs). This study investigated the effects of BMP-2 on the differentiation and production of proteoglycans in TDSCs in vitro. Rat patellar TDSCs were treated without or with BMP-2. The osteogenic, adipogenic, chondrogenic, and tenogenic differentiation of TDSCs were assessed by (1) Alizarin red-S staining assay; (2) Oil Red-O staining assay; (3) haematoxylin-eosin staining, Safranin-O staining, immunohistochemical staining of Sox9, and collagen type II; and (4) qRT-PCR analysis of lineage-specific markers. The production of glycoaminoglycans (GAG) in the BMP-2-treated TDSCs was assessed by alcian blue staining. The mRNA expression of aggrecan (Acan), decorin (Dcn), biglycan (Bgn), and fibromodulin (Fmod) in TDSCs after BMP-2 treatment was assessed by qRT-PCR. BMP-2 promoted the osteogenic, adipogenic, and chondrogenic differentiation but inhibited tenogenic marker expression of TDSCs. GAG production and Acan increased while Dcn, Bgn, and Fmod decreased in TDSCs after BMP-2 stimulation. In conclusion, BMP-2 promoted GAG deposition, aggrecan expression, and enhanced non-tenocyte differentiation of TDSCs in vitro. The effect of BMP-2 on TDSCs might provide insights into the histopathological changes of tendinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Animals, Outbred Strains
  • Biomarkers / metabolism
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • In Vitro Techniques
  • Male
  • Patellar Ligament / cytology
  • Patellar Ligament / metabolism
  • Proteoglycans / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Tendinopathy / metabolism*
  • Tendinopathy / pathology

Substances

  • Biomarkers
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Proteoglycans