Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF‐β Signaling Pathway

Abstract

Objective To investigate the effect and underlying mechanism of Bushenhuoxue (BSHX) formula on articular cartilage repair. Methods Twenty-four full-thickness cartilage defect rats were divided into two groups: model group and BSHX group (treated with BSHX formula). Macroscopic observation and histopathological study were conducted after 4- and 8-week treatment. Additionally, we also evaluated chondrocyte proliferation, extracellular matrix (ECM) deposition, cartilage degradation, and chondrocyte hypertrophy-related genes expression in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Moreover, we assessed aforementioned genes expression and pSMAD2/3 protein level in Tgfβr2 siRNA transfected chondrogenic ATDC5 cells in order to address whether BSHX formula exerts cartilage repairing effect through TGF-β signaling. Results Neocartilage regeneration promotion effect was observed in cartilage defect rats after BSHX formula treatment, with increases in Col2 and pSMAD2 and decreases in Mmp13 and Runx2. Moreover, cell proliferation, the elevated Col2a1, Aggrecan and pSMAD2/3, reduced Mmp13, Adamts5, Col10a1, and Runx2 expression were also observed in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Besides, the expression alteration of ECM deposition, cartilage degradation, chondrocyte hypertrophy-related genes, and pSMAD2/3 protein levels presented in Tgfβr2 downregulated chondrogenic ATDC5 cells couldn't be adjusted by BSHX formula treatment. Conclusion By activation of TGF-β signaling, BSHX formula can promote articular cartilage repair by accelerating chondrocyte proliferation and maintaining chondrocyte phenotype, upregulate ECM accumulation, and inhibit matrix degradation.

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway

“…It has been established that the COcontaining formulae and MR have similar biological effects, including anti-inflammatory (Yu and Wang, 2018;Yu et al, 2021), anti-oxidative stress (Xu et al, 2006), and anti-apoptotic properties, to mitigate degenerative diseases (Pi et al, 2017;Yu et al, 2021). In a previous study, we found that MR could effectively attenuate cartilage degeneration and arthritic development (Yu et al, 2021), comparable to the therapeutic effect of CO-composed TCM formulas (Zhang et al, 2017b;Wang et al, 2018a;Dong et al, 2018;Yang et al, 2019;. Furthermore, we recently demonstrated that the classic TCM formula Liuwei Dihuang Decoction (a COcontaining formula) could effectively impede IVDD progression by reversing the high expression of p53 protein in NP cells (Zhang et al, 2021c).…”

Efficacy and Safety of Intra-Articular Cell-Based Therapy for Osteoarthritis: Systematic Review and Network Meta-Analysis

“…34,39 The expression of TGF-β1 could promote extracellular matrix deposition and improve local cartilage regeneration. 44 Although this study did not find an advantage of chondrocytes compared to MSCs for OA treatment, the findings expand the cell-based therapies for OA. The safety of genetically modified cells that particularly concerning in the treatment of other diseases, such as stroke, 45 was demonstrated in the closed joint cavity microenvironment.…”

Naringin and bone marrow mesenchymal stem cells repair articular cartilage defects in rabbit knees through the transforming growth factor‑β superfamily signaling pathway

“…The TGF-β superfamily signaling pathway is important in the development of the growth plate and the formation of permanent articular cartilage. Previous studies have indicated that TGF-β plays an important regulatory role in the maintenance of the normal cartilage cell phenotype, as well as in the promotion of proliferating cells to differentiate into mature cartilage cells ( 52-54 ). Similarly, the TGF-β signaling pathway helps to maintain the cartilage cell phenotype and the stability of the cartilage tissue environment ( 55 ).…”