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Abstract
BackgroundWhile bone marrow-derived mesenchymal stem cells (BMSC) are established sources for stem cell-based cartilage repair therapy, articular cartilage-derived mesenchymal stem cells from osteoarthritis patients (OA-MSC) are new and potentially attractive candidates. We compared OA-MSC and BMSC in chondrogenic potentials, gene expression, and regulation by miR-365, a mechanical-responsive microRNA in cartilage (Guan et al., FASEB J 25: 4457–4466, 2011).MethodsTo overcome the limited number of OA-MSC, a newly established human OA-MSC cell line (Jayasuriya et al., Sci Rep 8: 7044, 2018) was utilized for analysis and comparison to BMSC. Chondrogenesis was induced by the chondrogenic medium in monolayer cell culture. After chondrogenic induction, chondrogenesis and mineralization were assessed by Alcian blue and Alizarin red staining respectively. MiRNA and mRNA levels were quantified by real-time PCR while protein levels were determined by western blot analysis at different time points. Immunohistochemistry was performed with cartilage-specific miR-365 over-expression transgenic mice.ResultsUpon chondrogenic induction, OA-MSC underwent rapid chondrogenesis in comparison to BMSC as shown by Alcian blue staining and activation of ACAN and COL2A1 gene expression. Chondrogenic induction also activated mineralization and the expression of hypertrophic and osteogenic genes in OA-MSC while only hypertrophic genes were activated in BMSC. MiR-365 expression was activated by chondrogenic induction in both OA-MSC and BMSC. Transfection of miR-365 in OA-MSC induced chondrogenic, hypertrophic, and osteogenic genes expression while miR-365 inhibition suppressed the expression of these genes. Over-expression of miR-365 upregulated markers of OA-MSC and hypertrophy and increased OA scores in adult mouse articular cartilage.ConclusionsInduction of chondrogenesis can activate mineralization, hypertrophic, and osteogenic genes in OA-MSC. MiR-365 appears to be a master regulator of these differentiation processes in OA-MSC during OA pathogenesis. These findings have important implications for cartilage repair therapy using cartilage derived stem cells from OA patients.
Highlights
While bone marrow-derived mesenchymal stem cells (BMSC) are established sources for stem cellbased cartilage repair therapy, articular cartilage-derived mesenchymal stem cells from osteoarthritis patients (OA-Mesenchymal stem cells (MSC)) are new and potentially attractive candidates
Mesenchymal stem cells Multiple cell lines of OA articular cartilage-derived mesenchymal stem cells (OA-MSC), normal articular cartilage-derived progenitor cell line 3, primary OA articular chondrocytes, and primary OASC were established after the use of discarded knee cartilage samples from patient surgery was approved by IRB as previously described [4]
Using multiple cell lines generated from the OA-MSC including the human OASC2 line used in this study, we showed that OA-MSCs are prone to chondrocyte hypertrophy, which was similar to BMSC [23,24,25]
Summary
While bone marrow-derived mesenchymal stem cells (BMSC) are established sources for stem cellbased cartilage repair therapy, articular cartilage-derived mesenchymal stem cells from osteoarthritis patients (OA-MSC) are new and potentially attractive candidates. Bone marrow-derived mesenchymal stem cells (BMSC) are one of the established stem cell sources for its capability of chondrogenic differentiation and formation of hyaline-like cartilage tissue [2]. Articular cartilage-derived mesenchymal stem cells from osteoarthritis patients (OA-MSC) are new and potentially attractive candidates for cell-based cartilage repair. They are readily available from surgery without immunological rejection for cell transplant [3]. To utilize OA-MSC for cartilage repair, further characterization is needed regarding its capacity for chondrogenesis and the key molecules that regulate this process
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