A.T., P.D., R.R., E.M. and J.V. are employed by Bioibérica S.A.
A.T., P.D., R.R., E.M, J.V., M.L.F., M.J.A. conceived and designed the experiments. M.L.F., M.C.T., M.C.C. performed the experiments. M.L.F., M.C.T., M.J.A. analysed the data and wrote the paper. All authors read and approved the final manuscript.
Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression.
We have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA.
Oral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption.
We have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.
Strom O, Borgstrom F, Kanis JA, Compston J, Cooper C, McCloskey EV, et al. Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2011;6(1–2):59–155. CrossRefPubMed
Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986;213(12):34–40. PubMed
Consensus Development Conference. Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med. 1993;94(6):646–50. CrossRef
Kim SK, Yoo TK, Oh E, Kim DW. Osteoporosis risk prediction using machine learning and conventional methods. Conf Proc IEEE Eng Med Biol Soc. 2013;2013:188–91. PubMed
Karvonen RL, Miller PR, Nelson DA, Granda JL, Fernandez-Madrid F. Periarticular osteoporosis in osteoarthritis of the knee. J Rheumatol. 1998;25(11):2187–94. PubMed
Feldkamp LA, Davis LC, Krettek C. Practical cone-beam algorithm. J Opt Soc Am A. 1984;1(1):612–9. CrossRef
Garnero P, Piperno M, Gineyts E, Christgau S, Delmas PD, Vignon E. Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage. Ann Rheum Dis. 2001;60(60):619–26. CrossRefPubMedPubMedCentral
Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2003;39(1–2):237–46.
Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis: Nat Rev. Rheumatol. 2010;6(11):625–35.
Oesser S, Seifert J. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell Tissue Res. 2003;311(3):393–9. PubMed
- Effects of BIS076 in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats
María Luisa Ferrándiz
María Carmen Terencio
María Carmen Carceller
María José Alcaraz
- BioMed Central
Neu im Fachgebiet Orthopädie und Unfallchirurgie
Mail Icon II