Andrographolide suppresses fibrogenic phenotype of chondrocytes and ameliorates osteoarthritis by regulating miR-137/BMP7 axis

J Orthop. 2024 Nov 26:64:108-116. doi: 10.1016/j.jor.2024.11.019. eCollection 2025 Jun.

Abstract

Background: Pathogenic degeneration of cartilage and the generation of fibrotic cartilage are crucial characteristics linked to the progression of osteoarthritis (OA). The current research aims to explore the potential function of the miR-137/BMP7 pathway in regulating the fibrogenic transition of chondrocytes associated with OA, as well as assess the therapeutic potential of andrographolide.

Methods: Samples of cartilage from the knees of patients with OA and individuals without OA were gathered to investigate the expression patterns of miR-137, BMP7, and markers associated with fibrosis. A cell model using primary chondrocytes stimulated with interleukin (IL)-1β was developed to study the involvement of the miR-137/BMP7 axis during the fibrogenic transition of these cells. Additionally, we utilized an animal model of OA in order to assess the beneficial effects of the anti-inflammatory natural compound andrographolide on the fibrogenesis induced by OA in vivo.

Results: Elevated levels of fibrogenic and inflammatory factors were linked to decreased miR-137 expression in OA samples. In IL-1β-treated chondrocytes, there was an upregulation of fibrogenic markers alongside a reduction in miR-137 levels. The overexpression of miR-137 inhibited fibrogenesis through the negative regulation of BMP7. Additionally, treatment with andrographolide was effective in attenuating the fibrogenic phenotype in chondrocytes and mitigating OA pathogenesis via modulating the miR-137/BMP7 pathway.

Conclusion: miR-137 downregulation and BMP7 overexpression might contribute to the fibrogenic features in OA-related chondrocytes. Andrographolide attenuates fibrogenic phenotype in chondrocytes and alleviates the severity of OA by modulating the miR-137/BMP7 axis.

Keywords: BMP7; Chondrocytes; Fibrosis; Osteoarthritis; miR-137.