Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection

Abstract

CONTEXT AND OBJECTIVE: The development of a slow and progressive mechanical model for osteoarthritis is important for correlation with clinical practice, and for evaluating the effects of disease-modifying medications. A mechanical osteoarthritis model was developed to evaluate the effects of intra-articular hyaluronic acid (HA) injection and oral diacerein administration. DESIGN AND SETTING: Experimental study at the Department of Orthopedics and Traumatology, Universidade de São Paulo. METHOD: Total medial meniscectomy was performed on seven groups of ten Wistar rats each, comprising four control groups (C) and three study groups (S). C.I: operated, non-medicated; C.II: operated, injections of HA vehicle; C.III: non-operated, non-medicated; C.IV: operated, non-medicated, sacrificed three months post-meniscectomy; S.I: operated, receiving intra-articular HA injections; S.II: operated, oral diacerein from the third to the seventh postoperative month; S.III: operated, received both medications. All the animals (except C.IV) were sacrificed seven months post-meniscectomy. All femurs and tibias were assessed histologically. RESULTS: The most severe degenerative histological changes were in the tibias of the operated knees. On the contralateral side, all groups had mild changes on the tibial surface. The femoral surface had slight changes. C.I showed severe changes. S.II results matched those of C.IV. HA protected the tibial surface. S.II and S.III had similar results. CONCLUSIONS: 1) The experimental model produced mild arthritis after three months and severe arthritis after seven months; 2) diacerein reduced the degenerative changes in both knees; 3) HA protected the joint cartilage; 4) Combining the two drugs did not improve the results.RESUMO CONTEXTO E OBJETIVO: Desenvolver um modelo osteoartrítico mecânico lento e progressivo é importante para correlação com a prática clínica e para avaliar os efeitos de medicamentos modificadores da doença. Um modelo mecânico de osteartrite foi desenvolvido para avaliar os efeitos de injeção intra-articular de hialuronato de sódio (AH) e de administração de diacereína oral. DESENHO E LOCAL: Estudo experimental no Departamento de Ortopedia e Traumatologia, Universidade de São Paulo. MÉTODO: Meniscectomia medial total foi feita em sete grupos de dez ratos Wistar, sendo quatro grupos controle (C) e três grupos estudo (E). C.I: operado, não medicado; C.II: operado, recebendo injeções do veículo do AH; C.III: não operado, não medicado; C.IV: operado, não medicado, sacrificado três meses pós-meniscectomia; EI: operado, recebendo injeções de AH intra-articular; E.II: operado, recebendo diacereína oral do terceiro ao sétimo mês pós-operatório; E.III: operado, recebeu ambas medicações. Todos os animais (exceto C.IV) foram sacrificados sete meses pós-meniscectomia. Todos os fêmures e tíbias foram analisados histologicamente. RESULTADOS: As alterações histológicas degenerativas mais graves encontram-se nas tíbias dos joelhos operados. No lado contra-lateral, todos os grupos apre...

A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis

“…J Arthritis 5: 193. doi:10.4172/2167-7921.1000193 Page 2 of 17 In rat and mouse, MMx surgery is usually conducted first by transecting the medial collateral ligament (MCL) fully or partially followed by wide opening of the knee capsule, and finally excising the medial meniscus [15,21,22]. Following the MMx procedure, a substantial subchondral bone changes occurred in rat knee at 8-weeks post-MMx as determined by μCT along with articular cartilage degeneration [23].…”

“…A number of genetically altered mice are also available at an increasing rate and are being used as surgically-induced OA models that provides a great deal of information on the genes playing role in OA [28]. MMx-induced knee OA is a common experimental procedure in mice and rats [15,21,22] that is to get the first-hand information on the effectiveness of therapeutical agent before testing it on large animals and or in human trials. MMx surgery conducted, on medial knee capsule, involved the following invasive steps, i.e., beginning with transecting MCL followed by dislodging the patella from the trochlear groove and diverting it laterally and exposing the knee capsule wide-open, and finally transecting the medial meniscus at entheses attachments [15,21,22].…”

“…MMx-induced knee OA is a common experimental procedure in mice and rats [15,21,22] that is to get the first-hand information on the effectiveness of therapeutical agent before testing it on large animals and or in human trials. MMx surgery conducted, on medial knee capsule, involved the following invasive steps, i.e., beginning with transecting MCL followed by dislodging the patella from the trochlear groove and diverting it laterally and exposing the knee capsule wide-open, and finally transecting the medial meniscus at entheses attachments [15,21,22]. Following the procedure that involved wide opening of knee capsule for MMx, substantial subchondral bone degeneration has been reported in MMx rat knee at 8-weeks post-MMx, as determined by μCT analysis [23].…”

“…Histological evaluation by H&E staining, proteoglycans, and collagen localization: Fibrillation and thinning of articular cartilage, in the knee joint, has been shown in experimentally induced OA in several species including rat and mouse [15,21,22], and human OA. The narrowing of space is a common feature in OA [2].…”

“…Knees and surrounding area was shaved, cleaned with iodine surgical scrub (7.5% iodine), 70% isopropanol and 10% Providone iodine (equivalent to 1% iodine) in sequence. MMx was conducted on the right knee (N=10) of the rat with less invasive approach as compared to the methods used by earlier researchers in rat or mouse [15,21,22]. Left knees served as unoperated controls (N=10).…”