BMP-7 modified exosomes derived from synovial mesenchymal stem cells attenuate osteoarthritis by M2 polarization of macrophages

Weixue Sun; Shaozheng Qu; Mingxia Ji; Yanli Sun; Baiqiang Hu

doi:10.1016/j.heliyon.2023.e19934

BMP-7 modified exosomes derived from synovial mesenchymal stem cells attenuate osteoarthritis by M2 polarization of macrophages

Heliyon. 2023 Sep 10;9(9):e19934. doi: 10.1016/j.heliyon.2023.e19934. eCollection 2023 Sep.

Authors

Weixue Sun¹, Shaozheng Qu², Mingxia Ji², Yanli Sun³, Baiqiang Hu⁴

Affiliations

¹ Joint Surgery and Sports Medicine Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, Shandong, China.
² Spinal Surgery Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, Shandong, China.
³ Orthopedics, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, Shandong, China.
⁴ Joint Surgery Department, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, Shandong, China.

Abstract

Background: Although the exosomes derived from mesenchymal stem cells (MSCs) display a therapeutic effect on inflammatory diseases, its application on OA has great limitations due to lack of specificity and targeting. The current study aimed to elucidate the potential therapeutic role of bone morphogenetic proteins-7(BMP-7) modified synovial mesenchymal stem cells-derived exosomes (SMSCs-exo) on OA and mechanism.

Methods: For in vitro experiments, LPS-treated macrophages RAW264.7 were treated with SMSCs-exo (exo) or BMP-7 modified SMSCs-exos (BMP-7-exo). The levels of inflammatory factors were assessed by ELISA. Also, the proportion of iNOS and CD206 positive cells were quantified by flow cytometry. Chondrocytes and RAW264.7 were co-culture to evaluate the effects of macrophage polarization on chondrocytes cellular behaviors. This effect on KOA was verified by an experiment in vivo. HE staining and Safranin fast green staining were used to observe the damage of articular cartilage. Immunohistochemistry was used to determine the expression of collagen II and aggrecan in articular cartilage, as well as the expression of iNOS and CD206 in synovial tissues.

Results: Our in vitro results showed that BMP-7-exo treatment promoted LPS-induced proliferation of macrophages and chondrocytes, and showed a better ability to reduce inflammation by promoting macrophages M2 polarization. After co-culture with LPS treated macrophages, the proliferation rate and migration of chondrocytes were significantly decreased, while the apoptosis was significantly increased. The macrophages treated with BMP-7-exo and exo partially reversed these changes. The chondrocytes in BMP-7-exo group had higher proliferation rate and migration, as well as lower apoptosis compared with the exo group. Also, the in vivo results showed BMP-7-exo treatment improved the pathological changes of KOA and promoted synovial macrophages M2 polarization.

Conclusions: Our results demonstrated that BMP-7-exo attenuated KOA inflammation and cartilage injury by synovial macrophages M2 polarization, suggesting that BMP-7-exo carry much therapeutic potential for OA.

Keywords: BMP-7; Exosomes; Inflammation; Macrophage polarization; Osteoarthritis; Targeted drug delivery.