Osteoarthritis (OA) causes articular cartilage destruction, initiating pain and inflammation in the joints, resulting in joint disability. Medications are available to manage these symptoms; however, their effects on the disease progression are limited. Loss of proteoglycans (PGs) was reported to contribute articular cartilage destruction in OA. Therapeutics approaches were previously studied in the animal models of OA. In the present study, we investigated the oral efficacy of four dosages of PGs (25 mg/kg, 50 mg/kg, 100 mg/kg and 200 mg/kg), isolated from the bramble shark cartilage, in an animal model of OA. Indomethacin was used as a bioequivalent formulation. Primarily, the mass spectrum analysis of the purified PGs obtained from bramble shark cartilage revealed the presence of two unique peptides including AGWLSDGSVR and LDGNPINLSK, that showed sequence similarity with aggrecan core-protein and epiphycan, respectively. The levels of C-reactive protein and uric acid in the OA rats were reduced when treated with PGs. Histopathology analysis displayed less cartilage erosion and neovascularization in OA rats treated with PGs. The X-ray imaging presented higher bone density with 200 mg/kg dosage of PG treatment in OA rats. The expressions of the inflammatory modulators including TNF-α, IL-1β, MMP13, NOS2, IL-10 and COX-2 were found to be moderated with PG treatment. In addition, PG treatment maintained the activities of antioxidant enzymes, including SOD and catalase in the joint tissues with a higher GSH content, in a dose-dependent manner. Taken together, our preliminary findings report the anti-osteoarthritic properties of PGs and recommend to evaluate its efficacy and safety in randomized trials.
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This study was supported by Ministry of Earth Sciences-Centre for Marine Living Resources and Ecology (MoES-CMLRE), Government of India (Grant no. MOES/10/MLR/01/2012) to MS and Mahidol University Post-Doctoral Fellowship Grant (Grant no. R016120002) to GPS.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Human and animal rights statement
Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), New Delhi, India and the Institutional Animal Ethics Committee (IAEC), ICAR-Central Institute of Fisheries Technology (ICAR-CIFT), Cochin, India (CIFT/B&N/IAEC/04/2013).
Boehme KA, Rolauffs B (2018) Onset and progression of human osteoarthritis-can growth factors, inflammatory cytokines, or differential miRNA expression concomitantly induce proliferation, ECM degradation, and inflammation in articular cartilage? Int J Mol Sci 19:2282. https://doi.org/10.3390/ijms19082282CrossRefGoogle Scholar
Carames B, Lopez-Armada MJ, Cillero-Pastor B, Lires-Dean M, Vaamonde C, Galdo F, Blanco FJ (2008) Differential effects of tumor necrosis factor-alpha and interleukin-1beta on cell death in human articular chondrocytes osteoarthritis and cartilage/OARS. Osteoarthr Res Soc 16:715–722. https://doi.org/10.1016/j.joca.2007.10.006CrossRefGoogle Scholar
Chun JM, Kim HS, Lee AY, Kim SH, Kim HK (2016) Anti-inflammatory and antiosteoarthritis effects of Saposhnikovia divaricata ethanol extract: in vitro and in vivo studies. Evi Based Complement Altern Med eCAM 2016:1984238. https://doi.org/10.1155/2016/1984238Google Scholar
Cifuentes DJ, Rocha LG, Silva LA, Brito AC, Rueff-Barroso CR, Porto LC, Pinho RA (2010) Decrease in oxidative stress and histological changes induced by physical exercise calibrated in rats with osteoarthritis induced by monosodium iodoacetate osteoarthritis and cartilage/OARS. Osteoarthr Res Soc 18:1088–1095. https://doi.org/10.1016/j.joca.2010.04.004CrossRefGoogle Scholar
Geusens P, Lems W (2008) Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis. Ther Clin Risk Manag 4:337–344CrossRefGoogle Scholar
Henrotin Y et al (2013) Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO(2)) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: a research study part of the Biovisco study. J Orthop Res 31:901–907. https://doi.org/10.1002/jor.22297CrossRefGoogle Scholar
Jung YK, Kim GW, Park HR, Lee EJ, Choi JY, Beier F, Han SW (2013) Role of interleukin-10 in endochondral bone formation in mice: anabolic effect via the bone morphogenetic protein/Smad pathway. Arthritis Rheum 65:3153–3164. https://doi.org/10.1002/art.38181CrossRefGoogle Scholar
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474CrossRefGoogle Scholar
Neame PJ, Sandy JD (1994) Cartilage aggrecan. Biosynthesis, degradation and osteoarthritis. J Fla Med Assoc 81:191–193Google Scholar
Neander G, Eriksson LO, Wallin-Boll E, Ersmark H, Grahnen A (1992) Pharmacokinetics of intraarticular indomethacin in patients with osteoarthritis. Eur J Clin Pharmacol 42:301–305CrossRefGoogle Scholar
Qin J et al (2013) Effect of Angelica sinensis polysaccharides on osteoarthritis in vivo and in vitro: a possible mechanism to promote proteoglycans synthesis. Evid Based Complement Alternat Med 2013:794761. https://doi.org/10.1155/2013/794761Google Scholar
Rehak NN, Janes G, Young DS (1977) Calorimetric enzymic measurement of uric acid in serum. Clin Chem 23:195–199Google Scholar
Rojas-Ortega M, Cruz R, Vega-Lopez MA, Cabrera-Gonzalez M, Hernandez-Hernandez JM, Lavalle-Montalvo C, Kouri JB (2015) Exercise modulates the expression of IL-1beta and IL-10 in the articular cartilage of normal and osteoarthritis-induced rats. Pathol Res Pract 211:435–443. https://doi.org/10.1016/j.prp.2015.01.008CrossRefGoogle Scholar
Yassin NZ, El-Shenawy SM, Abdel-Rahman RF, Yakoot M, Hassan M, Helmy S (2015) Effect of a topical copper indomethacin gel on inflammatory parameters in a rat model of osteoarthritis. Drug Des Devel Ther 9:1491–1498. https://doi.org/10.2147/DDDT.S79957Google Scholar