Session Type: Abstract Submissions (ACR)
Background/Purpose: Mohawk homeobox (MKX) has been demonstrated as a tendon and ligament specific transcriptional factor. MKX knock-out mice showed hypoplastic tendons throughout the body, due to reduced type I collagenproduction in tendon cells. Our group also demonstrated expression of MKX decreased in mature human knee ligament tissues, during joint aging and further decreased in osteoarthritis (OA). The aims of this study were to characterize factors that may promote tenogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs) and to investigate the role of MKX in ligament/tenogenic differentiation of BMMSCs.
Methods: Human BMMSCs (n=9 from 3 donors) were purchased from Lonza, and treated with putative tenogenic factors (50ng/ml BMP12, 5ng/ml TGFbeta or 50ng/ml PDGF). Tendon/ligament related gene expression was analyzed by qRT-PCR at 1-5 days after treatment. BMMSCs were infected with adenoviruses expressing MKX or Scleraxis (Scx), also a tendon specific transcription factor and tendon related gene expression was analyzed levels at days 1, 2 and 7.
Results: Basal MKX and SCX expression levels were low in BMMSCs. BMP12 increased expression of MKX and SCX genes in BMMSCs at day 5 (p<0.01, n=6). COL1a1 levels were higher in BMP12 and TGFbeta treated groups (p<0.01, n=6). Decorin (DCN) and tenascin B (TNXB), important extracellular matrix (ECM) components of ACL, were also higher in BMP12 treated group (p<0.05, n=6). The expression of COL1a1 and TNXB were increased by overexpression of MKX in BMMSCs (p<0.05, n=9). Tenomodulin (TNMD), a marker of late stage tenogenic differentiation, was expressed at higher levels in Ad-Mkx and Ad-Scx groups than in Ad-Mock group (p<0.05, n=9).
Conclusion: This is the first report to compare several potential tenogenic factors in BMMSCs and to investigate the MKX expression and function in human BMMSCs. The present findings demonstrate that BMP12 most effectively enhanced tenogenesis related genes including Mkx, and overexpression of MKX was associated with increased tendon ECM production. Thus, MKX is represents a key factor for tenogenic differentiation of BMMSCs.
M. K. Lotz,
Tanabe Research Laboratories,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tenogenic-effect-of-homeobox-mohawk-gene-for-bone-marrow-mesenchymal-stem-cells/