Chondrogenesis of human synovium-derived mesenchymal stem cells induced by kartogenin and transforming growth factors

Abstract

Purpose: To investigate if small molecule compound Kartogenin (KGN) can direct the differentiation of human synovium derived mesenchymal stem cells (SMSCs) into chondrocytes or increase the chondrogenic potential of tranforming growth factors. Methods: Human SMSCs were isolated from synovial membrane tissue harvested from 6 donors when they underwent total knee arthroplasty. 5 × 105 cells were centrifuged to form pellets and then incubated in control medium or chondrogenic medium. The chondrogenic medium was consisted of transforming growth factors with or without addition of KGN. The group in which pellets induced only by KGN was also setted. We also designed a group in which SMSCs were induced first with TGF-β3 for 1 week and then with KGN for 2 weeks. Pellets were induced for 21 days. Pellets size, hematoxylin and eosin staining, immunohistochemical staining for collagen type II, and cartilage specific gene epression were used to measure chondrogenic ability. Results: KGN alone could not induce human SMSCs into chondrocytes, but addition of KGN to the growth factors significantly increased chondrogenesis. Furthermore, human SMSCs induced with TGF-β3 first for 1 week and then with KGN for 2 weeks, exhibited similar chondrogenic capabilityas that of TGF-β3 with KGN or BMP-2. Conclusions: KGN is a promising additive for directing human SMSCs into chondrocytes. KGN can significantly enhance chondrocytes differentiation and proliferation in a cartilage microenvironment and may be a therapeutic option for cartilage lesions and early stage osteoarthritis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)