Department Orthopaedic Surgery, Exp. Orthopaedics, ZMB/Biopark 1, University of Regensburg, Regensburg, Germany.
Department Orthopaedic Surgery, Asklepiosklinikum, Bad Abbach, Germany.
Sci Rep. 2017 Oct 16;7(1):13297. doi: 10.1038/s41598-017-13567-x.
Osteoarthritis (OA) is characterized by a slowly progressing, irreversible loss of articular cartilage. Tissue engineering approaches for cartilage regeneration include stem cell-based strategies but not much is known about their repair capacity in an OA microenvironment. The aim of the present study was to identify factors regulating collagen expression during chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) in an OA microenvironment. Coculture with OA cartilage induced miR-29b expression in BMSC which inhibited collagen I and III expression. Elevated miR-29b expression resulted in higher caspase 3/7 activity and promoted apoptosis of BMSC in part by directly inhibiting the anti-apoptotic proteins Bcl-2 and Mcl-1. Stimulation with IFN-γ induced miR-29b expression in BMSC. Our results suggest that miR-29b affects BMSC-based OA cartilage regeneration because expression of collagen III, mainly produced by undifferentiated BMSC, and collagen I, a marker for dedifferentiated chondrocytes, are inhibited by miR-29b thus influencing composition of the newly formed ECM. This might be critical to avoid formation of inferior fibrocartilage instead of hyaline cartilage. Furthermore, higher miR-29b expression promotes apoptosis either preventing excessive cell growth or reducing the number of BMSC undergoing chondrogenesis. Thus, miR-29b has both supportive but possibly also unfavourable effects on BMSC-based OA cartilage regeneration.
骨关节炎（OA）的特征是关节软骨进行性、不可逆的丧失。用于软骨再生的组织工程方法包括基于干细胞的策略，但对于它们在 OA 微环境中的修复能力知之甚少。本研究的目的是鉴定在 OA 微环境中骨髓间充质干细胞（BMSC）软骨分化过程中调节胶原表达的因素。与 OA 软骨共培养诱导 BMSC 中 miR-29b 的表达，从而抑制胶原 I 和 III 的表达。miR-29b 的高表达导致 caspase 3/7 活性增加，并通过直接抑制抗凋亡蛋白 Bcl-2 和 Mcl-1 促进 BMSC 凋亡。IFN-γ 刺激 BMSC 中 miR-29b 的表达。我们的研究结果表明，miR-29b 影响基于 BMSC 的 OA 软骨再生，因为胶原 III 的表达，主要由未分化的 BMSC 产生，以及胶原 I，一种去分化软骨细胞的标志物，被 miR-29b 抑制，从而影响新形成的 ECM 的组成。这对于避免形成劣质纤维软骨而不是透明软骨可能是至关重要的。此外，miR-29b 表达增加促进了细胞凋亡，从而防止了细胞过度生长或减少了发生软骨形成的 BMSC 数量。因此，miR-29b 对基于 BMSC 的 OA 软骨再生既有支持作用，也可能有不利影响。
