Effect of Betula platyphylla var. japonica on Proteoglycan Release, Type II Collagen Degradation, and Matrix Metalloproteinase Expression in Rabbit Articular Cartilage Explants

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage, subchondral bond remodeling, spur formation, synovial inflammation, and in particular, the degradation of proteoglycan and collagen. The integrity of these macromolecules is vital to cartilage and joint function. 1)Proteoglycan is a component of the articular cartilage extracellular matrix, providing it with many of its characteristic physicochemical properties.2) The carbohydrate component of aggrecan, which constitutes at least 90% of its molecular mass, consists of many long keratin sulfate, chondroitin sulfate, and glycosaminoglycan (GAG) chains covalently linked to a core protein.3) The contribution of these GAG polymers to cartilage function can be divided into two categories: firstly, maintenance of hydration, a property dependent on their polyanionicity, which engenders in cartilage the ability to withstand compression, and secondly, interactions with other macromolecules that depend on the specific distribution of the negative charges of GAG and its carbohydrate backbone conformation. 4,5) Thus, the importance of these proteoglycans is clear. However, neither their specific role nor the mechanisms regulating their synthesis are fully understood.Collagen is another component of articular cartilage, and it is present primarily as type II collagen.6) It plays a role in maintaining the integrity of the cartilage matrix and allows proteoglycan to be held in the matrix. 7) Healthy cartilage maintains a dynamic equilibrium between processes that produce and processes that degrade matrix components. It is thought that this equilibrium is disturbed in OA, and that matrix-component degradative processes dominate, leading to an increased loss of the matrix. According to in vitro studies, collagen is much less readily released than proteoglycan, but collagen degradation results in the irreversible loss of structural integrity.8) There is circumstantial in vitro and in vivo evidence indicating a significant role for matrix metalloproteinases (MMPs) in cartilage destruction in arthritis. 9)MMPs can be classified into four subgroups: collagenases (MMP-1, -8, -13), stromyelins (MMP-3, -10, -11), gelatinases (MMP-2, -9), and membrane-type MMPs.10) MMPs are synthesized in response to cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-a, which is thought to be involved in the pathogenesis of arthritis. [10][11][12][13] MMPs are released as inactive proenzyme forms and are then activated by limited proteolysis of the propeptide domain by plasmin, kallikrein, or trypsin.10,14) MMP-3 is capable of cleaving aggrecan core protein, as well as type II collagen (in the aminoterminal telopeptide) in vitro, but it is not clear if it is involved in the degradation of these proteins in cartilage. 15,16) MMP-13 is expressed by normal and osteoarthritic chondrocytes, and has been localized to both rheumatoid and osteoarthritic cartilage.17) MMP-13 is the most efficient collagenase against type II collagen, sug...

Anti-inflammatory and anti-nociceptive effect of Betula platyphylla var. japonica in human interleukin-1β-stimulated fibroblast-like synoviocytes and in experimental animal models

“…It has been effective and safe during its long history of human use (Huh, 1999;Kim, 2000). Previously our studies reported that Betula platyphylla extracts prevented cartilage degradation in cartilage explants culture (Cho et al, 2006), and the n-butanol fraction of Betula platyphylla also decreased cartilage alternations through balance of MMPs/TIMP-1 in vivo model of osteoarthritis without toxicity . The degree of inflammation was evaluated on a scale from 0 to 5 by two pathologists blinded to the treatments.…”

“…It has been reported that the bark extract of Betula platyphylla has antioxidant and anticancer activities (Ju et al, 2004). We previously reported that the bark extract of Betula platyphylla inhibits the degradation of proteoglycan and collagen through the down regulation of MMP-3 and MMP-13 expressions and activities without affecting the viability or morphology of IL-1␣-stimulated rabbit articular cartilage explants (Cho et al, 2006). Following bioactivity-guided fractionation, the most potent cartilage-protective fraction from the bark of Betula platyphylla (BFBP) (the n-butanol fraction) was identified using the GAG assay in cartilage rabbit explant cultures; the reported BFBP has been shown to have protective effects against cartilage degradation in a collagenase-induced osteoarthritis rabbit model .…”

The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

“…The bark of AWB contains betulin, several triterpenes and phenolic compounds, such as diarylheptanoids and arylbutanoids, as active compounds. It has been reported that lupane triterpens from the bark of AWB have antiviral activity and that the extract of the bark of AWB has antioxidant, anticancer, hepatoprotective, chondroprotective and superoxide scavenging activities (Matsuda et al, 1998;Baltina et al, 2003;Zhang et al, 2003;Ju et al, 2004;Cho et al, 2006). However, it has not yet been studied if and how AWB suppresses the development of AD.…”

Protective effects of butanol fraction from Betula Platyphyla var. japonica on cartilage alterations in a rabbit collagenase-induced osteoarthritis

“…It has been reported that the bark extract of Betula platyphylla has antioxidant and anticancer activity (Ju et al, 2004). We previously reported that the bark extract of Betula platyphylla inhibits the degradation of proteoglycan and collagen through the down regulation of MMP-3 and MMP-13 expression and activities without affecting the viability or morphology of IL-1␣-stimulated rabbit articular cartilage explants (Cho et al, 2006). Following the bioactivity-guided fractionation, the most potent cartilage protective fraction, n-butanol fraction from the bark of Betula platyphylla (BFBP), had been identified using GAG assay in cartilage explant culture of rabbit.…”