Abstract
Bushen Zhuangjin Decoction (BZD), a well-known formulation in Traditional Chinese Medicine, has been widely used for the treatment of osteoarthritis (OA). Due to the poor intrinsic repair capacity of chondrocytes, promoting the proliferation of chondrocytes is an efficient treatment to delay the progression of cartilage degradation. The present study, therefore, focused on the effect of BZD on chondrocyte proliferation, exploring the mechanism of BZD on the inhibition of cartilage degradation. Chondrocytes isolated from the knee articular cartilage of Sprague Dawley rats were cultured and identified by type II collagen immunohistochemistry. It was found that BZD promoted chondrocyte viability in a dose- and time-dependent manner. To investigate if BZD promoted the chondrocyte viability by stimulating the cell cycle progression a flow cytometer was used, and the results showed that the percentage proportion of G0/G1 cells was significantly lower, and the percentage proportion of S cells was significantly higher, in treated cells compared with that in untreated cells. To gain insight into the mechanism underlying the effect of BZD on the cell cycle progression, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6 and p21 was measured by reverse transcription-polymerase chain reaction and western blotting, respectively. The mRNA and protein expression of cyclin D1, CDK4 and CDK6 in the BZD-treated chondrocytes was significantly upregulated, while the mRNA and protein expression of p21 was significantly downregulated, compared with that in the untreated chondrocytes. These results suggested that BZD promoted chondrocyte proliferation by accelerating G1/S transition, indicating that BZD is a potential therapeutic agent for the treatment of OA.
Highlights
Osteoarthritis (OA), a common chronic disease increasingly prevalent with age, is manifested by joint pain, stiffness, disability and/or swelling, and reduces the overall quality of life of affected individuals [1,2]
Bushen Zhuangjin Decoction (BZD) can nourish the kidney, soothe the liver, promote blood circulation and dispel wind, and acts against the pathogenesis of OA, with kidneys dominating bones and the liver governing tendons, according to the theory. It was found in the present study that BZD promoted chondrocyte viability in a dose‐ and time‐dependent manner by stimulating cell cycle progression, indicating that BZD is a potential therapeutic agent for the treatment of OA
Chondrocytes produce and maintain the extracellular matrix (ECM), which is responsible for providing the appropriate function to articular cartilage [18,19]
Summary
Osteoarthritis (OA), a common chronic disease increasingly prevalent with age, is manifested by joint pain, stiffness, disability and/or swelling, and reduces the overall quality of life of affected individuals [1,2]. An important feature of OA, is caused by the interplay of metabolic, genetic, biochemical and biomechanical factors. This degradation results in the imbalance of catabolism and anabolism, which degrades the structural and functional integrity of the extracellular matrix (ECM). The integrity of the ECM is regulated by chondrocytes, the only type of cell in cartilage [3]. The family of cyclin‐dependent kinases (CDKs) is one of the key regulators in the cell cycle process [4,5]. Multiple cell cycle genes have been implicated in chondrocyte proliferation, including cyclin D1, CDK4, CDK6 and p21, affecting G1 phase progression as well as S phase entry [7]
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