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Effects of ID-CBT5101 in Preventing and Alleviating Osteoarthritis Symptoms in a Monosodium Iodoacetate-Induced Rat Model

  • Sim, Boo-Yong (Traditional and Biomedical Research Center, Daejeon University) ;
  • Choi, Hak-Joo (Traditional and Biomedical Research Center, Daejeon University) ;
  • Kim, Min-Goo (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Jeong, Dong-Gu (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Lee, Don-Gil (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Yoon, Jong-Min (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Kang, Dae-Jung (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Park, Soobong (Research Laboratories, Ildong Pharmaceutical Company) ;
  • Ji, Joong-Gu (Department of Oriental Health Care, Joongbu University) ;
  • Joo, In-Hwan (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • Kim, Dong-Hee (Traditional and Biomedical Research Center, Daejeon University)
  • Received : 2018.03.28
  • Accepted : 2018.04.28
  • Published : 2018.07.28

Abstract

Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.

Keywords

References

  1. Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, et al. 2006. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr. Cartil. 14: 13-29. https://doi.org/10.1016/j.joca.2005.07.014
  2. Longo UG, Loppini M, Fumo C, Rizzello G, Khan WS, Maffulli N, et al. 2012. Osteoarthritis: new insights in animal models. Open Orthop. J. 6: 558-563. https://doi.org/10.2174/1874325001206010558
  3. Couture RR, Cuello AC. 1984. Studies on the trigeminal antidromic vasodilatation and plasma extravasation in the rat. J. Physiol. 346: 273-285. https://doi.org/10.1113/jphysiol.1984.sp015021
  4. Brody LT. 2015. Knee osteoarthritis: clinical connections to articular cartilage structure and function. Phys. Ther. Sport 16: 301-316. https://doi.org/10.1016/j.ptsp.2014.12.001
  5. Park S, Kim YS, Lee D, Kwon Y, Park J, Lee SY, et al. 2014. Efficacy and safety of HT008 and glucosamine sulfate in the treatment of knee osteoarthritis: a randomized double-blind trial. Korean J. Herbol. 29: 45-52.
  6. Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. 2003. Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol. Pathol. 31: 619-624. https://doi.org/10.1080/01926230390241800
  7. Ashraf S, Mapp PI, Burston J, Bennett AJ, Chapman V, Walsh DA. 2014. Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis. Ann. Rheum. Dis. 73: 1710-1718. https://doi.org/10.1136/annrheumdis-2013-203416
  8. Di Paola R, Fusco R, Impellizzeri D, Cordaro M, Britti D, Morittu VM, et al. 2016. Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats. Arthritis Res. Ther. 18: 291-302. https://doi.org/10.1186/s13075-016-1189-5
  9. Fernihough J, Gentry C, Malcangio M, Fox A, Rediske J, Pellas T, et al. 2004. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain 112: 83-93. https://doi.org/10.1016/j.pain.2004.08.004
  10. Puente LD, Betoret NV, Cortes MR. 2009. Evolution of probiotic content and color of apples impregnated with lactic acid bacteria. Vitae 16: 297-303.
  11. Abdel-Hafeez HM, Saleh ES, Tawfeek SS, Youssef IM, Abdel-Daim AS. 2016. Effects of probiotic, prebiotic, and synbiotic with and without feed restriction on performance, hematological indices and carcass characteristics of broiler chickens. Asian-Australas. J. Anim. Sci. 30: 672-682. https://doi.org/10.5713/ajas.16.0535
  12. Kumar R, Joshi SR. 2009. Probiotics: biotechnology in prolongation of life, pp. 187. In Mishra CS, Champagne P (eds.), Biotechnology Applications. International Publishing House, New Delhi.
  13. Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. 2011. Regulation of inflammation by short chain fatty acids. Nutrients 3: 858-876. https://doi.org/10.3390/nu3100858
  14. Vonsy JL, Ghandehari J, Dickenson AH. 2009. Differential analgesic effects of morphine and gabapentin on behavioural measures of pain and disability in a model of osteoarthritis pain in rats. Eur. J. Pain 13: 786-793. https://doi.org/10.1016/j.ejpain.2008.09.008
  15. McDougall JJ, Watkins L, Li Z. 2006. Vasoactive intestinal peptide (VIP) is a modulator of joint pain in a rat model of osteoarthritis. Pain 123: 98-105. https://doi.org/10.1016/j.pain.2006.02.015
  16. Gerwin N, Bendele AM, Glasson S, Carlson CS. 2010. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthr. Cartil. 18: S24-S34.
  17. Chung HJ, Cho L, Shin JS, Lee J, Ha IH, Park HJ, et al. 2014. Effects of JSOG-6 on protection against bone loss in ovariectomized mice through regulation of osteoblast differentiation and osteoclast formation. BMC Complement. Altern. Med. 14: 184. https://doi.org/10.1186/1472-6882-14-184
  18. Chu n JM, Kim HS, Lee AY, K im SH, K im HK. 2 016. A ntiinflammatory and antiosteoarthritis effects of Saposhnikovia divaricata ethanol extract: in vitro and in vivo studies. Evid. Based Complement. Alternat. Med. 2016: 1984238.
  19. Garnero P, Mazieres B, Gueguen A, Abbal M, Berdah L, Lequesne M, et al. 2005. Cross-sectional association of 10 molecular markers of bone, cartilage, and synovium with disease activity and radiological joint damage in patients with hip osteoarthritis: the ECHODIAH cohort. J. Rheumatol. 32: 697-703.
  20. Perruccio AV, Chandran V, Power JD, Kapoor M, Mahomed NN, Gandhi R. 2017. Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex? Osteoarthr. Cartil. 25: 53-59. https://doi.org/10.1016/j.joca.2016.08.001
  21. Bellucci F, Meini S, Cucchi P, Catalani C, Nizzardo A, Riva A, et al. 2013. Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis. Osteoarthr. Cartil. 21: 1774-1780. https://doi.org/10.1016/j.joca.2013.08.014
  22. Springall R, Amezcua-Guerra LM, Gonzalez-Pacheco H, Furuzawa-Carballeda J, Gomez-Garcia L, Marquez-Velasco R, et al. 2013. Interferon-gamma increases the ratio of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in peripheral monocytes from patients with coronary artery disease. PLoS One 8: e72291. https://doi.org/10.1371/journal.pone.0072291
  23. Dahlberg L, Billinghurst RC, Manner P, Nelson F, Webb G, Ionescu M, et al. 2000. Selective enhancement of collagenasemediated cleavage of resident type II collagen in cultured osteoarthritic cartilage and arrest with a synthetic inhibitor that spares collagenase 1 (matrix metalloproteinase 1). Arthritis Rheum. 43: 673-682. https://doi.org/10.1002/1529-0131(200003)43:3<673::AID-ANR25>3.0.CO;2-8
  24. Yang CC, Lin CY, Wang HS, Lyu SR. 2 013. Matrix metalloproteases and tissue inhibitors of metalloproteinases in medial plica and pannus-like tissue contribute to knee osteoarthritis progression. PLoS One 8: e79662. https://doi.org/10.1371/journal.pone.0079662
  25. Becher N, Hein M, Uldbjerg N, Danielsen CC. 2008. Balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the cervical mucus plug estimated by determination of free non-complexed TIMP. Reprod. Biol. Endocrinol. 6: 45. https://doi.org/10.1186/1477-7827-6-45
  26. Jeong YJ, Kim I, Cho JH, Park DW, Kwon JE, Jung MW, et al. 2015. Anti-osteoarthritic effects of the Litsea japonica fruit in a rat model of osteoarthritis induced by monosodium iodoacetate. PLoS One 10: e0134856. https://doi.org/10.1371/journal.pone.0134856
  27. Bove SE, Calcaterra SL, Brooker RM, Huber CM, Guzman RE, Juneau PL, et al. 2003. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthr. Cartil. 11: 821-830. https://doi.org/10.1016/S1063-4584(03)00163-8
  28. Lunenfeld B, Stratton P. 2013. The clinical consequences of an ageing world and preventive strategies. Best Pract. Res. Clin. Obstet. Gynaecol. 27: 643-659. https://doi.org/10.1016/j.bpobgyn.2013.02.005
  29. Redlich K, Smolen JS. 2012. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov. 11: 234-250. https://doi.org/10.1038/nrd3669
  30. Crofford LJ. 2013. Use of NSAIDs in treating patients with arthritis. Arthritis Res. Ther. 15: S2. https://doi.org/10.1186/ar3910
  31. Lanas A. 2009. Nonsteroidal antiinflammatory drugs and cyclooxygenase inhibition in the gastrointestinal tract: a trip from peptic ulcer to colon cancer. Am. J. Med. Sci. 338: 96-106. https://doi.org/10.1097/MAJ.0b013e3181ad8cd3
  32. Lee SG, Lee EJ, Park WD, Kim JB, Kim EO, Choi SW. 2012. Anti-inflammatory and anti-osteoarthritis effects of fermented Achyranthes japonica Nakai. J. Ethnopharmacol. 142: 634-641. https://doi.org/10.1016/j.jep.2012.05.020
  33. Zhang JM, An J. 2007. Cytokines, inflammation and pain. Int. Anesthesiol. Clin. 45: 27-37. https://doi.org/10.1097/AIA.0b013e318034194e
  34. Wittenberg RH, Willburger RE, Kleemeyer KS, Peskar BA. 1993. In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases. Arthritis Rheum. 36: 1444-1450. https://doi.org/10.1002/art.1780361017
  35. Kaneko S, Satoh T , Chiba J, Ju C, Inoue K, Kagawa J. 2000. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell. Mol. Ther. 6: 71-79. https://doi.org/10.1080/13684730050515796
  36. Sokolove J, Lepus CM. 2013. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther. Adv. Musculoskelet. Dis. 5: 77-94. https://doi.org/10.1177/1759720X12467868
  37. Felson DT. 2009. Developments in the clinical understanding of osteoarthritis. Arthritis Res. Ther. 11: 203. https://doi.org/10.1186/ar2531
  38. Bollet AJ, Nance JL. 1966. Biochemical findings in normal and osteoarthritic articular cartilage. II. Chondroitin sulfate concentration and chain length, water, and ash content. J. Clin. Invest. 45: 1170-1177. https://doi.org/10.1172/JCI105423
  39. Brocklehurst R, Bayliss MT, Maroudas A, Coysh HL, Freeman MA, Revell PA, et al. 1984. The composition of normal and osteoarthritic articular cartilage from human knee joints. With special reference to unicompartmental replacement and osteotomy of the knee. J. Bone Joint Surg. Am. 66: 95-106. https://doi.org/10.2106/00004623-198466010-00013
  40. Chou MC, Tsai PH, Huang GS, Lee HS, Lee CH, Lin MH, et al. 2009. Correlation between the MR T2 value at 4.7 T and relative water content in articular cartilage in experimental osteoarthritis induced by ACL transection. Osteoarthr. Cartil. 17: 441-447. https://doi.org/10.1016/j.joca.2008.09.009
  41. Grushko G, Schneiderman R, Maroudas A. 1989. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage. Connect. Tissue Res. 19: 149-176. https://doi.org/10.3109/03008208909043895
  42. Madry H, Luyten FP, Facchini A. 2012. Biological aspects of early osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 20: 407-422. https://doi.org/10.1007/s00167-011-1705-8
  43. Englund M, Roemer FW, Hayashi D, Crema MD, Guermazi A. 2012. Meniscus pathology, osteoarthritis and the treatment controversy. Nat. Rev. Rheumatol. 8: 412-419. https://doi.org/10.1038/nrrheum.2012.69
  44. Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, et al. 2001. The association of bone marrow lesions with pain in knee osteoarthritis. Ann. Intern. Med. 134: 541-549. https://doi.org/10.7326/0003-4819-134-7-200104030-00007

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