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Chinese scientists proposes a new strategy for the treatment of osteoarthritis

Osteoarthritis (OA) is a common degenerative disease that causes irreversible loss of articular cartilage. The etiology of osteoarthritis is complex and involves many factors, including genetics, acute injury, and chronic inflammation. According to public information, the number of arthritis patients in my country has reached 100 million in 2018. However, there is currently no effective treatment method in clinical practice.

Zhejiang University School of Medicine and the team of Wang Xiumei from the School of Materials Science and Technology of Tsinghua University jointly published an online publication in the journal Science Advances entitled: Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence Research paper in an osteoarthritis rat model.

This study proposes a new strategy for the treatment of osteoarthritis (OA) by inhibiting bone and joint aging and promoting cartilage regeneration. Biomaterials are used to construct a regenerative microenvironment that inhibits aging to rejuvenate cartilage damaged by OA. For the first time, miR-29b-5p, a miRNA related to cartilage aging in OA, was discovered and verified, and miR-29b-5p was delivered by in situ injection of self-assembled polypeptide nanofiber hydrogels with stem cell homing activity for sustained release, while recruiting internal Derived synovial mesenchymal stem cells (SMSCs).

Sustained miR-29b-5p delivery and recruitment of stem cells with subsequent differentiation into chondrocytes enabled successful cartilage repair and chondrocyte regeneration. This study shows that miRNA-based therapy has great potential to replace traditional surgery for osteoarthritis.

OA is typically characterized by progressive loss of cartilage and reduced lubricating synovial fluid, and cartilage breakdown due to senescence of chondrocytes during OA development. The research team demonstrated for the first time that miR-29b-5p is significantly down-regulated in OA cartilage, and its up-regulation inhibits the expression of matrix metalloproteinases and aging-related genes (P16INK4a/P21) through translocase 1 (TET1), effectively alleviating the status quo of OA articular cartilage. , slow down the aging process.

Subsequently, the team developed a stem cell-homing hydrogel-based miRNA delivery system SKP@miR (Figure 1). On the one hand, sustained delivery of miR-29b-5p can inhibit chondrocyte senescence and improve the imbalance between cartilage matrix synthesis and decomposition in OA joints, thereby inhibiting the continuous destruction of cartilage matrix by OA; on the other hand, SKP@miR SMSCs are recruited and induced to differentiate into chondrocytes, replenishing the damaged matrix with healthy chondrocytes to repair defects and form new cartilage without the use of exogenous stem cells.

Figure 1. Construction of the hydrogel-based miR-29b-5p delivery system SKP@miR. (A) RAD and RAD-SKP polypeptides self-assemble to form nanofibrous hydrogels, and agomir-29b-5p is distributed inside the hydrogel. (B) Formation of stable hydrogels by adjusting pH to neutrality.

Studies have shown that SKP@miR can inhibit the aging of articular chondrocytes and the decomposition of cartilage matrix in OA rats, promote the synthesis of cartilage matrix, improve joint wear and tear, and finally restore damaged joints to a state similar to normal joints (Figure 2).

Figure 2. SKP@miR delivery of miRNA significantly attenuates joint aging in rats

Overall, the strategy of using injectable hydrogels to deliver miRNAs to treat OA through anti-aging has a significant effect, which is more convenient and practical in clinical application, which is of great significance for the development of disease-modifying therapies for OA.

Dr. Zhu Jinjin from the Shaw Hospital Affiliated to Zhejiang University School of Medicine and Dr. Yang Shuhui from the School of Materials Science and Engineering of Tsinghua University are the co-first authors of the paper. Researcher Wang Xiumei from the School of Materials Science and Technology of Tsinghua University and Professor Xiang Qiang from the Shaw Hospital Affiliated to Zhejiang University School of Medicine are the co-corresponding authors. The collaborators include Academician Antonio G. Mikos of Rice University in the United States, etc. The research was also supervised by Professor Fan Shunwu, Director of the Department of Orthopedics at Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine.