Zhang Xiaowei, Wu Shili, Zhu Yong, Chu Cong-Qiu
Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, United States.
Section of Rheumatology, VA Portland Health Care System, Portland, OR, United States.
Front Med (Lausanne). 2021 Feb 12;8:622609. doi: 10.3389/fmed.2021.622609. eCollection 2021.
The lack of effective treatment options for osteoarthritis (OA) is mostly due to the very limited regenerative capacity of articular cartilage. Mesenchymal stem cells (MSCs) have been most extensively explored for cell-based therapy to induce cartilage regeneration for OA. However, current expanded MSC-based approaches have significant drawbacks. On the other hand, osteoarthritic joints contain chondrocyte progenitors and MSCs in several niches which have the potential yet fail to differentiate into chondrocytes for cartilage regeneration. One of the underlying mechanisms of the failure is that these chondrocyte progenitors and MSCs in OA joints are deficient in the activity of chondrogenic transcription factor SOX9 (SRY-type high-mobility group box-9). Thereby, replenishing with exogenous SOX9 would reactivate the potential of these stem cells to differentiate into chondrocytes. Cell-permeable, super-positively charged SOX9 (scSOX9) protein is able to promote hyaline-like cartilage regeneration by inducing chondrogenic differentiation of bone marrow derived MSCs . This scSOX9 protein can be administered into osteoarthritic joints by intra-articular injection. This one-step, cell-free supplement of exogenous SOX9 may harness the regenerative potential of the intrinsic MSCs within the joint cavity to stimulate cartilage regeneration in OA.
骨关节炎（OA）缺乏有效的治疗方案，主要是因为关节软骨的再生能力非常有限。间充质干细胞（MSCs）已被广泛探索用于基于细胞的疗法，以诱导OA的软骨再生。然而，目前基于扩增MSCs的方法存在显著缺点。另一方面，骨关节炎关节在几个微环境中含有软骨细胞祖细胞和MSCs，它们有分化为软骨细胞以实现软骨再生的潜力，但却未能实现。这种失败的潜在机制之一是，OA关节中的这些软骨细胞祖细胞和MSCs缺乏软骨形成转录因子SOX9（SRY型高迁移率族盒9）的活性。因此，补充外源性SOX9将重新激活这些干细胞分化为软骨细胞的潜力。细胞可渗透的、带超强正电荷的SOX9（scSOX9）蛋白能够通过诱导骨髓来源的MSCs向软骨细胞分化来促进透明样软骨再生。这种scSOX9蛋白可以通过关节内注射施用于骨关节炎关节。这种一步式、无细胞补充外源性SOX9的方法可能利用关节腔内内在MSCs的再生潜力来刺激OA中的软骨再生。
