Activating types 1 and 2 angiotensin II receptors modulate the hypertrophic differentiation of chondrocytes

• Renin–angiotensin system components are expressed during hypertrophic differentiation.
• AT1R is expressed intensely during chondrocyte proliferation.
• AT2R is expressed intensely in the hypertrophic phase.
• The expression of Col.X, MMP13 and Runx2 are repressed by activating AT1R.
• The expression of Col.X, MMP13 and Runx2 are enhanced by activating AT2R.

A local tissue-specific renin–angiotensin system (local RAS) has been identified in many organs. However, no report has described the role of a local RAS in the hypertrophic differentiation of chondrocytes. To examine the role of a local RAS in the hypertrophic differentiation, we activated angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) separately in the cell line ATDC5, which involves differentiation from mesenchymal stem cells to hypertrophic chondrocytes. Activation of AT1R suppressed and activation of AT2R enhanced the expression of markers of hypertrophic differentiation, including type X collagen, matrix metalloproteinase 13 and runt-related transcription factor 2.