title: 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.
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: C H
authors.initials: CH
authors.lastname: Ma
authors.affiliation: Department of Radiology, Tong Ji Hospital, Tong Ji University, Shanghai, CN.
authors.forename: Q
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: Y X
authors.initials: YX
authors.lastname: Yu
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: D
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: K R
authors.initials: KR
authors.lastname: Niu
authors.affiliation: Department of Orthopedic Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, CN.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Yi
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology*; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D054544:Arthroplasty, Subchondral; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006614:Hindlimb / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D015601:Injury Severity Score; D053509:Matrix Metalloproteinase 13 / Q000187:drug effects / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000601:surgery; D065840:Protective Factors; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D000068879:Adalimumab