title: TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs.
abstract: Osteoarthritis (OA), the most common rheumatic disease, is characterized by joint-space narrowing due to progressive cartilage degradation and alterations in subchondral bone and the synovial membrane. These articular disturbances can have severe consequences, including pain, disability and loss of joint architectural integrity. Although the aetiology of OA is not understood, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by damage-associated molecules are thought to be involved. In this Review, we examine the relationship between Toll-like receptor 4 (TLR4) and OA in cartilage as well as in other OA-affected tissues, such as subchondral bone and synovium. We also discuss the different TLR4 agonists associated with OA and their effects in joint tissues. Finally, we describe existing and novel strategies that might be used to develop TLR4-specific disease-modifying OA drugs (DMOADs).
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor, Catherine Cookson Building, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Bone and Joint Research Unit, Instituto de Investigación, Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Avenida Reyes Católicos, Madrid, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Villalvilla
authors.affiliation: Bone and Joint Research Unit, Instituto de Investigación, Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Avenida Reyes Católicos, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Largo
authors.affiliation: Servicio Galego de Saude (SERGAS), Santiago University Clinical Hospital, Neuroendocrine Interaction in Rheumatology and Inflammatory Diseases (NEIRID) Research Laboratory 9, Institute of Medical Research (IDIS), Building C, Level 2, Trav. Choupana s/n, 15706, Santiago de Compostela, Spain.
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
authors.affiliation: Bone and Joint Research Unit, Instituto de Investigación, Fundación Jiménez Díaz, Universidad Autónoma de Madrid (UAM), Avenida Reyes Católicos, Madrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
mesh_terms: D000818:Animals; D006801:Humans; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4