Exploiting Joint-Resident Stem Cells by Exogenous SOX9 for Cartilage Regeneration for Therapy of Osteoarthritis.
Exploiting Joint-Resident Stem Cells by Exogenous SOX9 for Cartilage Regeneration for Therapy of Osteoarthritis.
复制标题
利用外源性SOX 9诱导关节干细胞再生软骨治疗骨关节炎
DOI：
10.3389/fmed.2021.622609
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发表时间：
2021
影响因子：
3.9
通讯作者：
Chu CQ
中科院分区：
文献类型：
--
作者：
Zhang X;Wu S;Zhu Y;Chu CQ
骨关节炎（OA）缺乏有效的治疗方案主要是由于关节软骨的再生能力非常有限。间充质干细胞（MSCs）已被广泛用于细胞治疗，以诱导OA软骨再生。然而，目前体外扩展的基于msc的方法有明显的缺点。另一方面，骨关节炎关节中含有软骨细胞祖细胞和MSCs，它们有可能分化为软骨再生的软骨细胞，但不能分化为软骨细胞。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缺乏软骨转录因子SOX9 （sry型高迁移率组box-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。细胞渗透性、带超正电荷的SOX9 （scSOX9）蛋白能够通过诱导骨髓源间充质干细胞在体内的软骨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进入骨关节炎关节。这种一步无细胞补充外源性SOX9可能利用关节腔内内在MSCs的再生潜力来刺激OA软骨再生。
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 in vitro 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 in vivo. 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.
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影响因子：
--
作者：
Hong Y;Chen W;Du X;Ning H;Chen H;Shi R;Lin S;Xu R;Zhu J;Wu S;Zhou H
通讯作者：
Zhou H
影响因子：
4.6
作者：
Fellows CR;Williams R;Davies IR;Gohil K;Baird DM;Fairclough J;Rooney P;Archer CW;Khan IM
通讯作者：
Khan IM
影响因子：
33.7
作者：
Bajpayee, Ambika G.;Grodzinsky, Alan J.
通讯作者：
Grodzinsky, Alan J.
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.7
作者：
Cucchiarini, Magali;Orth, Patrick;Madry, Henning
通讯作者：
Madry, Henning