RESUMO
We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 µg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.
Assuntos
Adalimumab/farmacologia , Antirreumáticos/farmacologia , Osso e Ossos/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Ligamento Cruzado Anterior/cirurgia , Artrite Experimental/tratamento farmacológico , Artroplastia Subcondral , Osso e Ossos/metabolismo , Cartilagem Articular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Feminino , Membro Posterior/patologia , Membro Posterior/cirurgia , Imuno-Histoquímica , Escala de Gravidade do Ferimento , Metaloproteinase 13 da Matriz/efeitos dos fármacos , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite/cirurgia , Fatores de Proteção , Distribuição Aleatória , Ratos Sprague-DawleyRESUMO
AIM: To evaluate the therapeutic effects of domestic chicken collagen type II (CCII) on rat osteoarthritis (OA) and analyze concomitant changes in the level of Matrix metalloproteinase (MMP)-13, MMP-9, Cathepsin K and their mRNA as well as the tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA in articular cartilage of osteoarthritic rats. METHODS: Osteoarthritis models were surgically induced. Morphology of articular cartilage was done by haematoxylin and eosin staining and Mankin score was calculated, immunohistochemistry of MMP-13, MMP-9 and Cathepsin K was done by ABC method while the mRNA level for MMP-13, MMP-9, cathepsin K as well as TIMP-1 was evaluated by RT-PCR method. RESULTS: Oral administration of CCII reduced the morphological changes of osteoarthritic cartilage (shown by Mankin score), decreased levels of MMP-13, MMP-9, cathepsin K as well as their mRNA in articular cartilage from osteoarthritic rats while it exhibited no effect on TIMP-1 mRNA. CONCLUSION: Oral CCII reduced articular cartilage degradation of osteoarthritic rats and may probably be a potent drug candidate for OA treatment.