• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.503-513
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• 2019

Osteoarthritis is a chronic degenerative articular disorder. Formation of bone spurs, synovial inflammation, loss of cartilage, and underlying bone restructuring have been reported to be the main pathologic characteristics of osteoarthritis symptoms. The onset and progression of osteoarthritis are attributed to various inflammatory cytokines in joint tissues and fluids that are produced by chondrocytes and/or interact with chondrocytes, as well as to low-grade inflammation in intra-articular tissues. Disruption of the equilibrium between the synthesis and degradation of the cartilage of the joint is the major cause of osteoarthritis. Hence, developing a promising pharmacological tool to restore the equilibrium between the synthesis and degradation of osteoarthritic joint cartilage can be a useful strategy for effectively managing osteoarthritis. In this review, we provide an overview of the research results pertaining to the search for a novel candidate agent for osteoarthritis management via restoration of the equilibrium between cartilage synthesis and degradation. We especially focused on investigations of medicinal plants and natural products derived from them to shed light on the potential pharmacotherapy of osteoarthritis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.3
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• pp.241-251
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• 1991

During the condylar shaving procedure, the articular soft tissue cover can be removed. Author compaired the histological healing process of the articular soft tissue cover between the preservative and unpreservative group group with 45 New Zealand rabbits(Average wt. : about 2.5kg). In unpreservative group, the usual high condylar shave with the removal of soft tissue cover was performed. In the preservative group, the underlying bone, replaced in its original position and sutured. The animals were sacrified 1, 2, 3, 4, 6 weeks interval after operation. The specimens were fixed in 10% neutral formalin and decalcified, paraffin embedded and stained by Hematoxylin & Eosin, and Masson's trichrome. The obtained results were as follows. 1. The condyles of the both group were covered with an articular sop tissue layer. 2. The cartilage cells in subarticular layer has regular continuous patterns in the preservative group but frequently interrupted in the unpreservative group. 3. The incision made in the posterior part of the articular surface for the elevation of the articular soft tissue frequently caused a deformity such as the interruption of the subarticular layer of cartilage. 4. By the above findings, the preservation of articular sop tissue cover may be the effective operation method on concept of bone remodelling.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.204-210
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• 2006

Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

• Journal of Korean Foot and Ankle Society
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• v.11 no.2
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• pp.130-134
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• 2007

Purpose: To investigate the relationship between classification based on simple radiographic findings and arthroscopic findings of the cartilage lesions in medial degenerative arthritis of the ankle joint. Materials and Methods: We studied 41 ankles of 36 patients with asymmetrical narrowing of the medial joint space. Degenerative arthritis following fracture and those with generalized arthritic disease were excluded, but those with a history of ankle sprain were included. Standing radiographs of all patients were graded according to the Takakura classification and the Kellgren-Lawrence (K/L) classification. Arthroscopic findings were classified according to the depth, width, and anteroposterior dimension of articular cartilage damage. Results: According to the Takakura classification, 29 ankles were classified as stage II, 7 cases as stage IIIA and 2 cases as stage IIIB. According to our classification of arthroscopic findings of 29 ankles in stage II, 1 ankle was graded as Grade I, 3 ankles as grade II, 10 ankles as grade III, and 15 ankles as grade IV. Spearman correlation coefficient between Takakura classification and arthroscopic classification was 0.342 (P=0.028), and coefficient between K/L classification and arthroscopic classification was 0.480 (P=0.001). Conclusion: Degenerative changes of the articular cartilage are more advanced than radiographic findings in many patients with ankle degenerative arthritis with asymmetrical narrowing of medial joint space. Therefore, we conclude that more aggressive effort should be made for correct diagnosis and treatment of degenerative arthritis.

• BMB Reports
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• v.51 no.10
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• pp.508-513
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• 2018

Fibronectin fragments found in the synovial fluid of patients with osteoarthritis (OA) induce the catabolic responses in cartilage. Nuclear high-mobility group protein Box 1 (HMGB1), a damage-associated molecular pattern, is responsible for the regulation of signaling pathways related to cell death and survival in response to various stimuli. In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in normal cartilage. Although 29-kDa FN-f significantly reduced the HMGB1 expression at the mRNA and protein levels 6 h after treatment, the cytoplasmic level of HMGB1 was increased in chondrocytes treated with 29-kDa FN-f, which significantly inhibited the interaction of HMGB1 with Beclin-1, increased the interaction of Bcl-2 with Beclin-1, and decreased the levels of Beclin-1 and phosphorylated Bcl-2. In addition, the level of microtubule-associated protein 1 light chain 3-II, an autophagy marker, was down-regulated in chondrocytes treated with 29-kDa FN-f, whereas the effect was antagonized by mTOR knockdown. Furthermore, prolonged treatment with 29-kDa FN-f significantly increased the release of HMGB1 into the culture medium. These results demonstrated that 29-kDa FN-f inhibits chondrocyte autophagy by modulating the HMGB1 signaling pathway.

• Macromolecular Research
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• v.16 no.6
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• pp.517-523
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• 2008

A RGD (Arg-Gly-Asp) conjugated chitosan hydrogel was used as a cell-supporting scaffold for articular cartilage regeneration. Thermosensitive chitosan-Pluronic (CP) has potential biomedical applications on account of its biocompatibility and injectability. A RGD-conjugated CP (RGD-CP) copolymer was prepared by coupling the carboxyl group in the peptide with the residual amine group in the CP copolymer. The chemical structure of RGD-CP was characterized by $^1H$ NMR and FT IR. The concentration of conjugated RGD was quantified by amino acid analysis (AAA) and rheology of the RGD-CP hydrogel was investigated. The amount of bound RGD was $0.135{\mu}g$ per 1 mg of CP copolymer. The viscoelastic parameters of RGD-CP hydrogel showed thermo-sensitivity and suitable mechanical strength at body temperature for cell scaffolds (a> 100 kPa storage modulus). The viability of the bovine chondrocyte and the amount of synthesized glycosaminoglycans (GAGs) on the RGD-CP hydrogels were evaluated together with the alginate hydrogels as a control over a 14 day period. Both results showed that the RGD-CP hydrogel was superior to the alginate hydrogel. These results show that conjugating RGD to CP hydro gels improves cell viability and proliferation, including extra cellular matrix (ECM) expression. Therefore, RGD conjugated CP hydrogels are quite suitable for a chondrocyte culture and have potential applications to the tissue engineering of articular cartilage tissue.

• The Journal of Korean Physical Therapy
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• v.26 no.6
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• pp.418-424
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• 2014

Purpose: This study was performed to investigate the effect of joint mobilization on pain relief and cartilage repair in an induced osteoarthritis rat model by analyzing the expression of heat shock protein 70 in articular cartilage. Methods: MIA was injected into SD rats to induce osteoarthritis. These rats were divided into 4 groups: control group (n=30), no further treatment after the MIA injection ; experimental group I(n=30), performed swimming exercise after the MIA injection experimental group II (n=30), underwent joint mobilization after the MIA injection and experimental group III (n=30), performed swimming exercise and underwent joint mobilization after the MIA injection. For the histologic and pathophysiologic evaluation, safranin-O staining and for the immunohistochemical evaluation, the expression of HSP 70 in articular cartilage was analyzed 1, 7, 14, and 21 days after the MIA injection. Results: The inflammatory response and loss of tissue declined in experimental groups I and II over time, whereas the greatest decreases were noted in experimental group III. In the articular cartilage, low expression of HSP 70 was observed in every group on day 1, whereas HSP 70 expression was elevated on days 7 and 14 in experimental groups II and III. After 21 days, experimental group II displayed the strongest positive reaction, whereas HSP 70 was higher in experimental group III at this time point compared to that after 14 days. Conclusion: Our results showed that swimming exercise and joint mobilization had positive effects on pain relief and histologic and functional recovery in an induced osteoarthritis rat model.

• Journal of Korean Orthopaedic Sports Medicine
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• v.4 no.1
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• pp.1-5
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• 2005

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.4
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• pp.364-367
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• 2006

In order to enhance the repair of defects in articular cartilage via cell therapy with autologous chondrocytes, as well as with periosteum-derived progenitor cells (PDPCs), silkworm hemolymph (SH) and a variety of cartilage-specific extracellular matrices (ECMs) including type II collagen, proline, chondroitin 4-sulfate, and chondroitin 6-sulfate were assessed with regard to their efficacy as media supplements. SH, a known anti-apoptotic agent, was found to enhance cell growth, as was shown by the results of a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. According to the results of reverse transcriptase polymerase chain reaction (RT-PCR) analyses, the cartilage-specific ECMs were found to stimulate the expression of hyaline cartilage-specific genes, most notably type II collagen and Sox9, in monolayer cultures of PDPCs.

• Biomedical Science Letters
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• v.8 no.3
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• pp.195-202
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• 2002

Osteoarthritis (OA), the most common form of arthritis, involves the destabilization of the normal balance between the degradation and the synthesis of articular cartilage and subchondral bone within a joint. As articular cartilage degrades over time, its smooth surface roughens and bone-against-bone contact ensues, producing the inflammation response symptomatic of this 'wear and tear' disease. Although a variety of genetic, developmental, metabolic, and traumatic factors may initiate the development of osteoarthritis, its symptoms (joint pain, stiffness, and curtailed function) typically evolve slowly, and patients experience periods of relative calm alternation with episodes of inflammation and pain. Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology characterized by chronic synovitis and cartilage destruction, affect 1% of the total population. Cartilage is a specialized connective tissue in which the chondrocytes occupy only 5% of the volume. Cartilage is particularly rich in extracellular matrix, with matrix making up 90% of the dry weight of the tissue chondrocytes have cell processes that extend a short distance into the matrix, but do not touch other cells thus in cartilage, cell-matrix interactions are essential for the maintenance of the extracellular matrix. In this study, subtractive hybridization method was utilized to detect genes differentially expressed in chondrocytes treated with methylprednisolone. We have isolated 57 genes that expressed differentially in the chondreocytes by methylprednisolone. 13 clones of them were analyzed with sequencing and their homologies were searched. 8 cDNAS included KIAA 0368, upregulated during skeletal muscle growth 5 (usmg 5), ribosomal protein S 18 (RPS 18), skeletal muscle ryanodine receptor, radial spoke protein 3 (RSP 3), ribosomal protein QM, ribosomal protein L37a (RPL37A), cytochrome coxidase subunit VIII (COX8).