Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2013

Open Access 01-02-2013 | Research article

Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis

Authors: Takuya Naraoka, Yasuyuki Ishibashi, Eiichi Tsuda, Yuji Yamamoto, Tomomi Kusumi, Satoshi Toh

Published in: Arthritis Research & Therapy | Issue 1/2013

Login to get access

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 and, second, to explore a synergetic effect with hyaluronan (HA).

Methods

Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four 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 was 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 osteoarthritis 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-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected.

Conclusion

Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.
Appendix
Available only for authorised users
Literature
1.
go back to reference Pelletier JP, Martel-Pelletier J, Abramson SB: Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001, 44: 1237-1247. 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F.CrossRefPubMed Pelletier JP, Martel-Pelletier J, Abramson SB: Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001, 44: 1237-1247. 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F.CrossRefPubMed
2.
go back to reference Aigner T, McKenna L: Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002, 59: 5-18. 10.1007/s00018-002-8400-3.CrossRefPubMed Aigner T, McKenna L: Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002, 59: 5-18. 10.1007/s00018-002-8400-3.CrossRefPubMed
3.
go back to reference Aigner T, Stove J: Collagens-major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. Adv Drug Deliv Rev. 2003, 55: 1569-1593. 10.1016/j.addr.2003.08.009.CrossRefPubMed Aigner T, Stove J: Collagens-major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. Adv Drug Deliv Rev. 2003, 55: 1569-1593. 10.1016/j.addr.2003.08.009.CrossRefPubMed
4.
go back to reference Aumailley M, Gayraud B: Structure and biological activity of the extracellular matrix. J Mol Med (Berl). 1998, 76: 253-265. 10.1007/s001090050215.CrossRef Aumailley M, Gayraud B: Structure and biological activity of the extracellular matrix. J Mol Med (Berl). 1998, 76: 253-265. 10.1007/s001090050215.CrossRef
5.
go back to reference Buckwalter JA, Mankin HJ: Articular cartilage repair and transplantation. Arthritis Rheum. 1998, 41: 1331-1342. 10.1002/1529-0131(199808)41:8<1331::AID-ART2>3.0.CO;2-J.CrossRefPubMed Buckwalter JA, Mankin HJ: Articular cartilage repair and transplantation. Arthritis Rheum. 1998, 41: 1331-1342. 10.1002/1529-0131(199808)41:8<1331::AID-ART2>3.0.CO;2-J.CrossRefPubMed
6.
go back to reference Vitagliano L, Berisio R, Mazzarella L, Zagari A: Structural bases of collagen stabilization induced by proline hydroxylation. Biopolymers. 2001, 58: 459-464. 10.1002/1097-0282(20010415)58:5<459::AID-BIP1021>3.0.CO;2-V.CrossRefPubMed Vitagliano L, Berisio R, Mazzarella L, Zagari A: Structural bases of collagen stabilization induced by proline hydroxylation. Biopolymers. 2001, 58: 459-464. 10.1002/1097-0282(20010415)58:5<459::AID-BIP1021>3.0.CO;2-V.CrossRefPubMed
7.
go back to reference Takahashi K, Goomer RS, Harwood F, Kubo T, Hirasawa Y, Amiel D: The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta (IL-1β), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage. 1999, 7: 182-190. 10.1053/joca.1998.0207.CrossRefPubMed Takahashi K, Goomer RS, Harwood F, Kubo T, Hirasawa Y, Amiel D: The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta (IL-1β), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage. 1999, 7: 182-190. 10.1053/joca.1998.0207.CrossRefPubMed
8.
go back to reference Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J: Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum. 1997, 40: 1653-1661. 10.1002/art.1780400915.CrossRefPubMed Moldovan F, Pelletier JP, Hambor J, Cloutier JM, Martel-Pelletier J: Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum. 1997, 40: 1653-1661. 10.1002/art.1780400915.CrossRefPubMed
9.
go back to reference Julovi SM, Ito H, Nishitani K, Jackson CJ, Nakamura T: Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res. 2011, 29: 258-264. 10.1002/jor.21216.CrossRefPubMed Julovi SM, Ito H, Nishitani K, Jackson CJ, Nakamura T: Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res. 2011, 29: 258-264. 10.1002/jor.21216.CrossRefPubMed
10.
go back to reference Hiraoka N, Takahashi KA, Arai Y, Sakao K, Mazda O, Kishida T, Honjo K, Tanaka S, Kubo T: Intra-articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase-13 in osteoarthritic subchondral bone. J Orthop Res. 2011, 29: 354-360. 10.1002/jor.21240.CrossRefPubMed Hiraoka N, Takahashi KA, Arai Y, Sakao K, Mazda O, Kishida T, Honjo K, Tanaka S, Kubo T: Intra-articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase-13 in osteoarthritic subchondral bone. J Orthop Res. 2011, 29: 354-360. 10.1002/jor.21240.CrossRefPubMed
11.
go back to reference Amiel D, Toyoguchi T, Kobayashi K, Bowden K, Amiel ME, Healey RM: Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model. Osteoarthritis Cartilage. 2003, 11: 636-643. 10.1016/S1063-4584(03)00119-5.CrossRefPubMed Amiel D, Toyoguchi T, Kobayashi K, Bowden K, Amiel ME, Healey RM: Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model. Osteoarthritis Cartilage. 2003, 11: 636-643. 10.1016/S1063-4584(03)00119-5.CrossRefPubMed
12.
go back to reference Sakai Y, Yamato R, Onuma M, Kikuta T, Watanabe M, Nakayama T: Non-antigenic and low allergic gelatin produced by specific digestion with an enzyme-coupled matrix. Biol Pharm Bull. 1998, 21: 330-334. 10.1248/bpb.21.330.CrossRefPubMed Sakai Y, Yamato R, Onuma M, Kikuta T, Watanabe M, Nakayama T: Non-antigenic and low allergic gelatin produced by specific digestion with an enzyme-coupled matrix. Biol Pharm Bull. 1998, 21: 330-334. 10.1248/bpb.21.330.CrossRefPubMed
13.
go back to reference Pesakova V, Novotna J, Adam M: Effect of the tripeptide glycyl-l-histidyl-l-lysine on the proliferation and synthetic activity of chick embryo chondrocytes. Biomaterials. 1995, 16: 911-915. 10.1016/0142-9612(95)93115-T.CrossRefPubMed Pesakova V, Novotna J, Adam M: Effect of the tripeptide glycyl-l-histidyl-l-lysine on the proliferation and synthetic activity of chick embryo chondrocytes. Biomaterials. 1995, 16: 911-915. 10.1016/0142-9612(95)93115-T.CrossRefPubMed
14.
go back to reference Tsuruoka N, Yamato R, Sakai Y, Yoshitake Y, Yonekura H: Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur. Biosci Biotechnol Biochem. 2007, 71: 2680-2687. 10.1271/bbb.70287.CrossRefPubMed Tsuruoka N, Yamato R, Sakai Y, Yoshitake Y, Yonekura H: Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur. Biosci Biotechnol Biochem. 2007, 71: 2680-2687. 10.1271/bbb.70287.CrossRefPubMed
15.
go back to reference Setton LA, Elliott DM, Mow VC: Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. 1999, 7: 2-14. 10.1053/joca.1998.0170.CrossRefPubMed Setton LA, Elliott DM, Mow VC: Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. 1999, 7: 2-14. 10.1053/joca.1998.0170.CrossRefPubMed
16.
go back to reference Sah RL, Yang AS, Chen AC, Hant JJ, Halili RB, Yoshioka M, Amiel D, Coutts RD: Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament. J Orthop Res. 1997, 15: 197-203. 10.1002/jor.1100150207.CrossRefPubMed Sah RL, Yang AS, Chen AC, Hant JJ, Halili RB, Yoshioka M, Amiel D, Coutts RD: Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament. J Orthop Res. 1997, 15: 197-203. 10.1002/jor.1100150207.CrossRefPubMed
17.
go back to reference McDevitt CA, Muir H: Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog. J Bone Joint Surg Br. 1976, 58: 94-101.PubMed McDevitt CA, Muir H: Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog. J Bone Joint Surg Br. 1976, 58: 94-101.PubMed
18.
go back to reference Yoshioka M, Coutts RD, Amiel D, Hacker SA: Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage. 1996, 4: 87-98. 10.1016/S1063-4584(05)80318-8.CrossRefPubMed Yoshioka M, Coutts RD, Amiel D, Hacker SA: Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage. 1996, 4: 87-98. 10.1016/S1063-4584(05)80318-8.CrossRefPubMed
19.
go back to reference Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KP: The OARSI histopathology initiative-recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage. 2010, 18 (Suppl 3): S53-S65.CrossRefPubMed Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KP: The OARSI histopathology initiative-recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage. 2010, 18 (Suppl 3): S53-S65.CrossRefPubMed
20.
go back to reference Ohara H, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima S: Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol. 2010, 37: 330-338. 10.1111/j.1346-8138.2010.00827.x.CrossRefPubMed Ohara H, Ichikawa S, Matsumoto H, Akiyama M, Fujimoto N, Kobayashi T, Tajima S: Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts. J Dermatol. 2010, 37: 330-338. 10.1111/j.1346-8138.2010.00827.x.CrossRefPubMed
21.
go back to reference Mariggio MA, Cassano A, Vinella A, Vincenti A, Fumarulo R, Lo Muzio L, Maiorano E, Ribatti D, Favia G: Enhancement of fibroblast proliferation, collagen biosynthesis and production of growth factors as a result of combining sodium hyaluronate and aminoacids. Int J Immunopathol Pharmacol. 2009, 22: 485-492.PubMed Mariggio MA, Cassano A, Vinella A, Vincenti A, Fumarulo R, Lo Muzio L, Maiorano E, Ribatti D, Favia G: Enhancement of fibroblast proliferation, collagen biosynthesis and production of growth factors as a result of combining sodium hyaluronate and aminoacids. Int J Immunopathol Pharmacol. 2009, 22: 485-492.PubMed
22.
go back to reference Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F, Nagashima Y, Ikezawa Z, Aihara M: Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model. J Dermatol Sci. 2012, 66: 136-143. 10.1016/j.jdermsci.2012.02.004.CrossRefPubMed Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F, Nagashima Y, Ikezawa Z, Aihara M: Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model. J Dermatol Sci. 2012, 66: 136-143. 10.1016/j.jdermsci.2012.02.004.CrossRefPubMed
23.
go back to reference Huang B, Li CQ, Zhou Y, Luo G, Zhang CZ: Collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering. J Biomed Mater Res B Appl Biomater. 2009, 92: 322-331. Huang B, Li CQ, Zhou Y, Luo G, Zhang CZ: Collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering. J Biomed Mater Res B Appl Biomater. 2009, 92: 322-331.
Metadata
Title
Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis
Authors
Takuya Naraoka
Yasuyuki Ishibashi
Eiichi Tsuda
Yuji Yamamoto
Tomomi Kusumi
Satoshi Toh
Publication date
01-02-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4181

Other articles of this Issue 1/2013

Arthritis Research & Therapy 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.