[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Collagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis (OA) and, second, to explore a synergetic effect with hyaluronan (HA). METHODS: Osteoarthritis was induced by anterior cruciate ligament transaction (ACLT) of the right knee in seventy-two Japanese white rabbits and they were divided into 4 groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 (MMP-13) were also analyzed immunohistochemically. A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results. RESULTS: All treatment groups exhibited slightly higher resistance to the progression of OA than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp and Ctp/HA treated groups had significantly increased type II collagen-positive chondrocytes at the 5th week after the surgery, although the numbers of MMP-13-positive chondrocytes were not affected. CONCLUSION: Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by ACLT in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.
Arthritis research & therapy 02/2013; 15(1):R32. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.
Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3).
Expression of IL-6 was mainly seen in phases I, II and III, collagen type 1 in phase II, MMP-1, 2 in phase III, and decorin, TGF-β1 and α-smooth muscle actin in phase IV. Histologically, degradation and scar formation were seen in the ACL remnant after phase III. The numbers of CD55 and P-Stat3 positive cells were elevated from phase II to phase III.
Elevated cell numbers including P-Stat3 positive cells were not related to collagens but to MMPs' expressions.
[Show abstract][Hide abstract] ABSTRACT: Tumor-necrosis factor-alpha (TNF-alpha) is a potent proinflammtory cytokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Retinoic acid-inducible gene-I (RIG-I) is a DExH box protein, which is known to play a role in the inflammatory and immune reactions. We previously reported about potential involvement of RIG-I in synovial inflammation in RA. In the present study, we demonstrated the expression of RIG-I in fibroblast-like synoviocytes stimulated with TNF-alpha. RNA interference against interferon (IFN)-beta abolished the TNF-alpha-induced RIG-I expression. In addition, knockdown of RIG-I partially inhibited the TNF-alpha-induced expression of CC chemokine ligand (CCL) 5, a chemokine with chemotactic activity toward lymphocytes and monocytes. These findings suggest that the TNF-alpha/IFN-beta/RIG-I/CCL5 pathway may be involved in the pathogenesis of synovial inflammation in RA.
[Show abstract][Hide abstract] ABSTRACT: Proteoglycans are one of the most important components of the extracellular matrix in the cartilage and the levels of proteoglycans. such as versican and aggrecan, increase during chondrogenesis. The purpose of this study was to investigate the effect of exogenous proteoglycans from salmon nasal cartilage on chondrogenesis of mesenchymal stem cells. Mesenchymal stem cells derived from bone marrow aspiration of rabbit femurs were induced to chondrogenic lineage using a pellet culture technique. Pellets were cultured in the medium with or without cell growth factors. with or without proteoglycans. or a combination of these agents. Pellets treated with cell growth factors became hypertrophic and showed lacuna formation. and synthesis of cartilage matrix was recognized histologically. The expression of type II collagen and aggrecan mRNA were decreased in pellets incubated with a combination of cell growth factors and proteoglycans, compared to those incubated with only cell growth factors. Exogenous proteoglycans may down-regulate the expression of cartilage-specific mRNA directly, or may interact with growth factors in the culture medium. As the increase of glycoprotein during chondrogenesis is important for determining the direction and degree of differentiation. exogenous proteoglycans may have a similar effect.