SHORT LINK N ACTS AS A DISEASE MODIFYING OSTEOARTHRITIS DRUG

被引:7
作者
Antoniou, J. [1 ,2 ]
Epure, L. M. [2 ]
Grant, M. P. [2 ]
Richard, H. [3 ]
Sampalis, J. [2 ]
Roughley, P. J. [2 ]
Laverty, S. [3 ]
Mwale, F. [1 ,2 ]
机构
[1] SMBD Jewish Gen Hosp, Lady Davis Inst Med Res, Orthopaed Res Lab, Montreal, PQ, Canada
[2] McGill Univ, Fac Med, Dept Expt Surg, Montreal, PQ, Canada
[3] Univ Montreal, Fac Med Vet, Dept Sci Clin, Comparat Orthoped Res Lab, St Hyacinthe, PQ, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Osteoarthritis; cartilage repair; tissue engineering; bioactive peptides; short link N; ARTICULAR-CARTILAGE; TERMINAL PEPTIDE; RABBIT MODEL; PROTEIN; PROTEOGLYCAN; COLLAGEN; BIOSYNTHESIS; DEGRADATION; ARTHRITIS; MATRIX;
D O I
10.22203/eCM.v037a21
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Osteoarthritis (OA) is a degenerative joint disease characterised by a progressive degradation of articular cartilage and underlaying bone and is associated with pain and disability. Currently, there is no medical treatment to reverse or even retard OA. Based on our previous reports, where we establish the repair potential of short Link N (sLN) in the intervertebral disc, a cartilage-like tissue, we hypothesise that sLN may hold similar promises in the repair of articular cartilage. This study aimed to determine if sLN, could prevent OA disease progression. Skeletally mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) of their left femorotibial joints to induce joint degeneration typical of OA. Beginning 3 weeks post-operatively, and every three weeks thereafter for 12 weeks, either saline (1 mL) or sLN (100 mu g in 1 mL saline) was injected intraarticularly into the operated knee. Six additional rabbits underwent sham surgery but without ACLT or post-operative injections. The effects on gross joint morphology and cartilage histologic changes were evaluated. In the Saline group, prominent erosion of articular cartilage occurred in both femoral condyle compartments and the lateral compartment of the tibial plateau while, sLN treatment reduced the severity of the cartilage damage in these compartments of the knee showing erosion. Furthermore, statistically significant differences were detected between the joint OA score of the saline and sLN treated groups (p = 0.0118). Therefore, periodic intraarticular injection of sLN is a promising nonsurgical treatment for preventing or retarding OA progression, by reducing cartilage degradation.
引用
收藏
页码:347 / 359
页数:13
相关论文
共 39 条
[31]   BMP receptor signaling is required for postnatal maintenance of articular cartilage [J].
Rountree, RB ;
Schoor, M ;
Chen, H ;
Marks, ME ;
Harley, V ;
Mishina, Y ;
Kingsley, DM .
PLOS BIOLOGY, 2004, 2 (11) :1815-1827
[32]   BMP signalling in skeletal development, disease and repair [J].
Salazar, Valerie S. ;
Gamer, Laura W. ;
Rosen, Vicki .
NATURE REVIEWS ENDOCRINOLOGY, 2016, 12 (04) :203-221
[33]   Association between expression of the Bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome [J].
Schmal, Hagen ;
Niemeyer, Philipp ;
Zwingmann, Joern ;
Stoffel, Fabian ;
Suedkamp, Norbert P. ;
Mehlhorn, Alexander T. .
BMC MUSCULOSKELETAL DISORDERS, 2010, 11
[34]   Periodic Knee Injections of BMP-7 Delay Cartilage Degeneration Induced by Excessive Running in Rats [J].
Sekiya, Ichiro ;
Tang, Tao ;
Hayashi, Masaya ;
Morito, Toshiyuki ;
Ju, Young-Jin ;
Mochizuki, Tomoyuki ;
Muneta, Takeshi .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2009, 27 (08) :1088-1092
[35]   Validation of a 40 MHz B-scan ultrasound biomicroscope for the evaluation of osteoarthritis lesions in an animal model [J].
Spriet, MP ;
Girard, CA ;
Foster, SF ;
Harasiewicz, K ;
Holdsworth, DW ;
Laverty, S .
OSTEOARTHRITIS AND CARTILAGE, 2005, 13 (02) :171-179
[36]   Bone morphogenetic protein 7 (bmp-7) stimulates Proteoglycan synthesis in human osteoarthritic chondrocytes in vitro [J].
Stoeve, J. ;
Schneider-Wald, B. ;
Scharf, H. -P. ;
Schwarz, M. L. .
BIOMEDICINE & PHARMACOTHERAPY, 2006, 60 (10) :639-643
[37]   Effect of oral glucosamine on cartilage degradation in a rabbit model of osteoarthritis [J].
Tiraloche, G ;
Girard, C ;
Chouinard, L ;
Sampalis, J ;
Moquin, L ;
Ionescu, M ;
Reiner, A ;
Poole, AR ;
Laverty, S .
ARTHRITIS AND RHEUMATISM, 2005, 52 (04) :1118-1128
[38]   ISSLS Prize Winner: Effect of Link Protein Peptide on Human Intervertebral Disc Cells [J].
Wang, Zili ;
Hutton, William C. ;
Yoon, S. Tim .
SPINE, 2013, 38 (17) :1501-1507
[39]   Characterization of a model of osteoarthritis in the rabbit knee [J].
Yoshioka, M ;
Coutts, RD ;
Amiel, D ;
Hacker, SA .
OSTEOARTHRITIS AND CARTILAGE, 1996, 4 (02) :87-98