OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is elevated in the serum and synovial fluid of patients with osteoarthritis (OA). This study was undertaken to investigate the potential role of MIF in OA in human joint tissues and in vivo in mice with age-related and surgically induced OA. METHODS: MIF in conditioned media from human chondrocytes and meniscal cells and from cartilage explants was measured by enzyme-linked immunosorbent assay. The severity of OA was analyzed histologically in male wild-type and MIF-/- mice at 12 and 22 months of age and following destabilization of the medial meniscus (DMM) surgery in 12-week-old MIF-/- mice as well as in wild-type mice treated with a neutralizing MIF antibody. Synovial hyperplasia was graded in S100A8-immunostained histologic sections. Bone morphometric parameters were measured by micro-computed tomography. RESULTS: Human OA chondrocytes secreted 3-fold higher levels of MIF than normal chondrocytes, while normal and OA meniscal cells produced equivalent amounts. Compared to age- and strain-matched controls, the cartilage, bone, and synovium in older adult mice with MIF deletion were protected against changes of naturally occurring age-related OA. No protection against DMM-induced OA was seen in young adult MIF-/- mice or in wild-type mice treated with anti-MIF. Increased bone density in 8-week-old mice with MIF deletion was not maintained at 12 months. CONCLUSION: These results demonstrate a differential mechanism in the pathogenesis of naturally occurring age-related OA compared to injury-induced OA. The inhibition of MIF may represent a novel therapeutic target in the reduction of the severity of age-related OA.
OBJECTIVE:Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is elevated in the serum and synovial fluid of patients with osteoarthritis (OA). This study was undertaken to investigate the potential role of MIF in OA in human joint tissues and in vivo in mice with age-related and surgically induced OA. METHODS:MIF in conditioned media from human chondrocytes and meniscal cells and from cartilage explants was measured by enzyme-linked immunosorbent assay. The severity of OA was analyzed histologically in male wild-type and MIF-/- mice at 12 and 22 months of age and following destabilization of the medial meniscus (DMM) surgery in 12-week-old MIF-/- mice as well as in wild-type mice treated with a neutralizing MIF antibody. Synovial hyperplasia was graded in S100A8-immunostained histologic sections. Bone morphometric parameters were measured by micro-computed tomography. RESULTS:Human OA chondrocytes secreted 3-fold higher levels of MIF than normal chondrocytes, while normal and OA meniscal cells produced equivalent amounts. Compared to age- and strain-matched controls, the cartilage, bone, and synovium in older adult mice with MIF deletion were protected against changes of naturally occurring age-related OA. No protection against DMM-induced OA was seen in young adult MIF-/- mice or in wild-type mice treated with anti-MIF. Increased bone density in 8-week-old mice with MIF deletion was not maintained at 12 months. CONCLUSION: These results demonstrate a differential mechanism in the pathogenesis of naturally occurring age-related OA compared to injury-induced OA. The inhibition of MIF may represent a novel therapeutic target in the reduction of the severity of age-related OA.
Authors: Albert C Chen; Michele M Temple; Darren M Ng; Nicole Verzijl; Jeroen DeGroot; Johan M TeKoppele; Robert L Sah Journal: Arthritis Rheum Date: 2002-12
Authors: Marita Cross; Emma Smith; Damian Hoy; Sandra Nolte; Ilana Ackerman; Marlene Fransen; Lisa Bridgett; Sean Williams; Francis Guillemin; Catherine L Hill; Laura L Laslett; Graeme Jones; Flavia Cicuttini; Richard Osborne; Theo Vos; Rachelle Buchbinder; Anthony Woolf; Lyn March Journal: Ann Rheum Dis Date: 2014-02-19 Impact factor: 19.103
Authors: R Kleemann; A Hausser; G Geiger; R Mischke; A Burger-Kentischer; O Flieger; F J Johannes; T Roger; T Calandra; A Kapurniotu; M Grell; D Finkelmeier; H Brunner; J Bernhagen Journal: Nature Date: 2000-11-09 Impact factor: 49.962
Authors: E N Blaney Davidson; A Scharstuhl; E L Vitters; P M van der Kraan; W B van den Berg Journal: Arthritis Res Ther Date: 2005-09-30 Impact factor: 5.156
Authors: Margaret A McNulty; Richard F Loeser; Cynthia Davey; Michael F Callahan; Cristin M Ferguson; Cathy S Carlson Journal: Cartilage Date: 2011-10 Impact factor: 4.634
Authors: Dave Ewart; Lindsey Harper; Amy Gravely; Richard A Miller; Cathy S Carlson; Richard F Loeser Journal: Connect Tissue Res Date: 2019-09-18 Impact factor: 3.417
Authors: Huseyin Ozkan; Martina Di Francesco; Helen Willcockson; José Valdés-Fernández; Valentina Di Francesco; Froilán Granero-Moltó; Felipe Prósper; Paolo Decuzzi; Lara Longobardi Journal: Drug Deliv Transl Res Date: 2022-09-15 Impact factor: 5.671
Authors: Richard F Loeser; Liubov Arbeeva; Kathryn Kelley; Anthony A Fodor; Shan Sun; Veronica Ulici; Lara Longobardi; Yang Cui; Delisha A Stewart; Susan J Sumner; M Andrea Azcarate-Peril; R Balfour Sartor; Ian M Carroll; Jordan B Renner; Joanne M Jordan; Amanda E Nelson Journal: Arthritis Rheumatol Date: 2022-01-04 Impact factor: 10.995
Authors: Austin V Stone; Richard F Loeser; Michael F Callahan; Margaret A McNulty; David L Long; Raghunatha R Yammani; Sara Bean; Kadie Vanderman; Susan Chubinskaya; Cristin M Ferguson Journal: Cartilage Date: 2020-09-17 Impact factor: 3.117
Authors: Jacqueline T Hecht; Alka C Veerisetty; Juliana Wu; Francoise Coustry; Mohammad G Hossain; Frankie Chiu; Francis H Gannon; Karen L Posey Journal: Am J Pathol Date: 2021-06-08 Impact factor: 5.770