Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

Abstract

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.

Does progranulin account for the opposite effects of etanercept and infliximab/adalimumab in osteoarthritis?

“…In this way, Etanercept may be blocking PGRN's protective and anti‐inflammatory effect against the development of OA. This would explain the detrimental effects of Etanercept in OA observed by Olson et al Unlike Etanercept, mouse TNFα monoclonal antibody (Infliximab, Remicade) and humanized TNFα monoclonal antibody (Adalimumab, Humira) are specific for TNFα, and have been shown to be protective against the development of OA in animal models . This is supported by clinical trials in which Infliximab and Adalimumab have been reported to alleviate symptoms of OA .…”

İntraartiküler propolis ekstraktının erişkin sıçanlarda deneysel osteoartrit tedavisinde etkinliği

“…SF grubuna ise aynı işlem 0.1 ml serum fizyolojik uygulanarak yapıldı. [5][6][7][8]19,21 . İlave olarak bazı sitokinler özellikle MMP'ları (MMP1, MMP3 ve MMP13) gibi birçok proteolitik enzimin sentezini ve salınımını da arttırır.…”

“…İlave olarak bazı sitokinler özellikle MMP'ları (MMP1, MMP3 ve MMP13) gibi birçok proteolitik enzimin sentezini ve salınımını da arttırır. Yine TNFα, IL1, IL17 ve IL18 gibi sitokinler de aynı zamanda MMP inhibitörlerini de azaltırlar [5][6][7][8]21 . İnflamatuvar sitokinlerin kondrositler, sinoviyal hücreler, eklem ve eklem çevresi dokular üzerine olan etkilerinden başka immun sistem hücrelerini de etkileyip inflamasyon sahasına migrasyonlarını sağlayıcı özellikleri vardır.…”

“…Bu sitokinler matriks metalloproteinazları (MMP) ve katabolik enzimlerin kondrositlerden salınımını arttırarak normal eklem kıkırdağı döngüsündeki katabolik süreci arttırır ve dejenerasyonu da hızlandırırlar. Bunun yanı sıra özellikle IL'ler MMP inhibitörlerini de azaltarak normal eklem kıkırdağı döngüsündeki anabolik süreci de yavaşlatırlar [5][6][7][8] .…”

The role of progranulin in arthritis

“…Increasing evidence indicates that OA is also a chronic inflammatory and immunological disease . Additionally, the application of TNF has a therapeutic effect in multiple OA animal models . Moreover, targeting TNF‐α has been shown to alleviate symptoms in patients with OA .…”