The molecular mechanism of treating osteoarthritis with dipsacus saponins by inhibiting chondrocyte apoptosis

Abstract

Abstract. The present study aimed to determine the molecular mechanism of treating osteoarthritis with dipsacus saponins by inhibiting the apoptosis of chondrocytes. A total of 30 New Zealand rabbits were randomly divided into 2 groups: A control group and a model group. The osteoarthritis model was established using the HULTH method. The success of the model establishment was determined by pathological morphology and measurement of inflammatory cytokine levels. Chondrocytes were isolated and divided into 4 groups treated with varying concentrations of dipsacus saponins: 0, 25, 50 and l00 µg/l dipsacus saponins. Cell cycle distribution was analyzed using flow cytometry. Changes in cyclin D1, cyclin-dependent kinase 4 (CDK4) and p21 expression were detected by western blotting and changes in the levels of Bcl-2, Bax, caspase-3 and caspase-9 mRNA were detected using reverse transcription-quantitative polymerase chain reaction. The osteoarthritis model was established successfully, indicated by a significant increase in the levels of IL-1β, IL-6 and TNF-α in the model group (P<0.05) compared with the control group. The viability of the chondrocytes increased following treatment with dipsacus saponins in a concentration-dependent manner. The number of chondrocytes in the G0/G1 phase decreased in the 50 and l00 µg/l groups while the number of chondrocytes in the G2/M phase increased in the 50 and l00 µg/l groups. Levels of cyclin D1 and CDK4 expression increased following treatment with dipsacus saponins. Levels of Bax, caspase-3 and caspase-9 expression decreased while Bcl-2 levels increased following treatment with dipsacus saponins. The viability of chondrocytes increased following treatment with dipsacus saponins in a concentration-dependent manner. Thus, dipsacus saponins inhibited the apoptosis of chondrocytes by up-regulating Bcl-2 and down-regulating caspase-9, caspase-3 and Bax expression.

Hydrogen sulfide inhibits endoplasmic reticulum stress through the GRP78/mTOR pathway in rat chondrocytes subjected to oxidative stress

“…Chondrocytes (CHs), the only cell type present in cartilage, are responsible for the development of cartilage ( 4 , 5 ). CHs produce and maintain the extracellular matrix, which normally has a low turnover rate.…”

“…The release of inflammatory cytokines into the synovial fluid stimulates the production of pro-inflammatory cytokines, which could contribute to the pathology of OA (2,3). chondrocytes (cHs), the only cell type present in cartilage, are responsible for the development of cartilage (4,5). cHs produce and maintain the extracellular matrix, which normally has a low turnover rate.…”

“…The widespread use of non-steroidal anti-inflammatory drugs is accompanied by an increase in gastrointestinal reactions, which affects the survival of patients. To overcome bioavailability and stability issues, intra-articular injections with small molecules are rapidly cleared from the joint within hours via synovial vasculature and larger macromolecules within days via synovial lymphatics (5)(6)(7). However, drugs for OA have limited success and display challenges with obtaining effective drug loading and release profiles persist (8,9).…”

Cell Growth Inhibition of Saponin XII from Dipsacus japonicus Miq. on Acute Myeloid Leukemia Cells

“…The results indicate that this compound inhibits the cell growth of OCI-AML cells by an increase of apoptosis—a known effect of saponins that is exerted through caspase 3/8/9 activation [ 13 , 21 ]. This effect is shown in particular by Dipsacus saponins as previous studies demonstrate that Dipsacus saponins decrease apoptosis by increasing the anti-apoptotic molecule Bcl-2, decreasing the expression of pro-apoptotic molecules Bax, caspase-9 and caspase-8 [ 22 ], and by decreasing proliferation. Due to a limited amount of the studied compound, it was not possible to perform studies on structure–activity relationships.…”

Evaluation of the Clinical Effect of Modified Dipsacus Decoction in the Treatment of Osteoporotic Fractures

“…All of them increase the levels of blood calcium, blood phosphorus, osteocalcin, etc. ; natural copper can replenish trace elements such as copper, iron, zinc, manganese, etc., which can further increase collagen content and promote the formation of callus [12][13][14][15] . Based on the results of this article, the total clinical treatment effectiveness of the observation group was 96.67%, the fracture healing time was significantly shorter than that of the control group, and bone density and laboratory indicators were significantly improved, suggesting that combined Chinese and Western medicine treatment has higher application advantages, exerting a synergistic effect to further improve the efficiency of clinical treatment and speed up fracture healing.…”