PTH (1-34) enhances the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes by inhibiting proinflammatory cytokines expression on OA chondrocyte repair in vitro

Abstract

Background: The effects of bone marrow mesenchymal stem cells (BMSCs) during the treatment of cartilage damage have been proven to be attributed to paracrine mechanisms, particularly the effect of exosomes. Exosomes from different batches are inhomogeneous, and different treatment effects are observed between samples. The purpose of this research was to find more effective and homogeneous exosomes for the repair of chondrocytes in osteoarthritis (OA). We observed the potential effects and possible mechanisms of exosomes derived from parathyroid hormone (PTH) (1-34)-preconditioned BMSCs (Exo^PTH) in the alleviation of OA.

Materials and methods: Exosomes derived from BMSCs (Exo^BMSC) and Exo^PTH were isolated by differential centrifugation. Primary rat chondrocytes were used to establish the OA model by interleukin 1 beta (IL-1β) in vitro. The effects of these two types of exosomes on OA chondrocyte proliferation, migration, apoptosis, and extracellular matrix formation were measured and compared. We observed changes in IL-2, TNF-α, and IL-6 levels via Western blotting (WB), and quantitative real-time PCR (qRT-PCR).

Results: We successfully extracted Exo^BMSC and Exo^PTH and established an IL-1β-induced OA model in primary chondrocytes from rats. Our study showed that IL-2, TNF-α, and IL-6 levels increased significantly in OA chondrocytes; however, both Exo^BMSC and Exo^PTH reduced the levels of IL-2, TNF-α, and IL-6. In addition, Exo^PTH exhibited stronger anti-inflammatory effects. Exo^PTH had a more marked effect on proliferation, migration, and production of the extracellular matrix (Col-II) in OA chondrocytes than Exo^BMSC at 24 h.

Conclusion: Exo^PTH increased the migration, proliferation, and chondral matrix formation of OA chondrocytes in vitro. In OA chondrocyte therapy, the potential mechanism of Exo^PTH might involve the inhibition of production of proinflammatory cytokines. Although the two types of exosomes had some similar effects, most effects of Exo^PTH were better than those of Exo^BMSC, so Exo^PTH may have a better ability to alleviate OA.

Keywords: Chondrocyte; Exosome; Osteoarthritis; Parathyroid hormone.