Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our findings may provide new insights in MSCs intra-articular injection for OA treatment.

关节内注射间充质干细胞 (MSCs) 是治疗骨关节炎 (OA) 的一种很有前景的策略。然而，越来越多的研究表明，注射的MSCs在关节腔内的粘附、迁移和存活能力较差。最近的一项研究表明，原弹性蛋白 (TE) 作为可溶性添加剂调节 MSCs 的粘附、增殖和表型维持，表明 TE 可以促进 MSCs 在再生医学中的归巢。在本研究中，我们使用 TE 作为注射介质，并将其与 MSCs 关节内注射中的经典介质进行比较，例如生理盐水 (NS)、透明质酸 (HA) 和富含血小板的血浆 (PRP)。我们发现 TE 可以有效提高附着力、迁移、在间接共培养系统中，髌下脂肪垫间充质干细胞 (IPFP-MSCs) 的软骨形成分化和增强骨关节炎软骨细胞 (OACs) 的基质合成。此外，TE可以通过激活整合素β1、ERK1/2和纽蛋白（VCL）显着增强IPFP-MSCs的粘附体外。此外，关节内注射 TE-IPFP MSCs 悬浮液导致 IPFP-MSCs 存活率的短期增加和更好的大鼠关节组织的组织学评分。抑制整合素 β1 或 ERK1/2 减弱了体内TE-IPFP MSCs 悬浮液的保护作用。总之，TE 通过增强细胞粘附和激活整合素 β1/ERK/VCL 通路来促进 IPFP-MSC 的性能并保护膝关节软骨免受 OA 损伤。我们的发现可能为 MSCs 关节内注射治疗 OA 提供新的见解。