Shockwaves Inhibit Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Association with Adenosine and A2B Receptors

Sci Rep. 2017 Oct 30;7(1):14377. doi: 10.1038/s41598-017-14875-y.

Abstract

Extracorporeal shockwave therapy (ESWT) has emerged as the important choice for the treatment of many orthopedic disorders. Our previous mechanistic studies suggest that ESWT promoted osteogenesis of human mesenchymal stem cells (hMSCs) through mechanisms that involve adenosine 5'-triphosphate (ATP) release. In this study, we investigated the effect of ESWT on chondrogenesis of hMSCs. We demonstrate that ESWT treatment caused a significant release of adenosine from hMSCs; ESWT treatment increased the levels of A2B receptor (A2BR) in hMSCs under 3-D culture conditions. ESWT, exogenous adenosine and specialized A2BR agonist suppressed hMSC chondrogenic differentiation through downregulating the expressions of aggrecan (ACAN), Collagen Type I alpha 2(COL1A2), Collagen Type II alpha 1(COL2A1), Sex-Determining Region YBox 9 (SOX9) and Sex-Determining Region YBox 6 (SOX6). Selective A2BR antagonists induced chondrogenic differentiation of hMSCs. This study indicated that shockwave therapy inhibits hMSC chondrogenic differentiation through or partially through regulation of adenosine release and activation of A2B receptor under 3-D culture conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adult
  • Aggrecans / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chondrogenesis / drug effects*
  • Collagen / metabolism
  • Extracorporeal Shockwave Therapy / methods*
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Middle Aged
  • Osteogenesis / drug effects
  • Receptor, Adenosine A2B / drug effects
  • Receptor, Adenosine A2B / metabolism

Substances

  • Aggrecans
  • Receptor, Adenosine A2B
  • Collagen
  • Adenosine