Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Abstract

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.

Elucidation of the Underlying Mechanism of Gujian Oral Liquid Acting on Osteoarthritis through Network Pharmacology, Molecular Docking, and Experiment

“…Notably, GJ treatment could significantly change the expressions of col2, MMP13, IL-1 β , and TNF- α , suggesting its contribution to inflammation and extracellular matrix degradation. Simultaneously, our results showed the therapeutic effects of GJ on the aberrant subchondral bone structure and gait post DMM surgery, most of which was in accord with previous reports [ 37 , 38 ].…”

Integrated Analysis of Transcriptome Changes in Osteoarthritis: Gene Expression, Pathways and Alternative Splicing

“…13 Recent investigation into OA shows articular chondrocyte homeostasis could be disrupted by overweight, aging as well as genetic alterations in tumor growth factor (TGF)-β/Smad, Wnt/β-catenin, and Ihh signaling pathways. [14][15][16][17] The upregulation of catabolic enzymes like matrix metalloproteinases (MMP)-13 and ADAMTS5 in most mouse models of OA suggest that these enzymes may serve as the potential therapeutic targets in the intervention of the progression of the OA. 18 Recently, with the development of high-throughput sequencing technology, more and more studies have attempted to find the possible and potential mechanism of the pathogenesis and progression of OA by performing multi-omics sequencing.…”

16S rDNA analysis of osteoporotic rats treated with osteoking

“…Compared to anti-OP medications such as diphosphonate and HRT, TCM itself rarely has side-effects and is cheaper. TCM appears to be more acceptable for patients with chronic OP and osteoking could improve OP with regard to both anti-resorption of bone and osteogenesis [44].…”