title: The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis.
abstract: Mounting evidence suggests reconceptualizing osteoarthritis (OA) as an inflammatory disorder. Trauma and obesity, the common risk factors of OA, could trigger the local or systemic inflammatory cytokines cascade. Inflammatory bone loss has been well documented; yet it remains largely unknown about the link between the inflammation and hypertrophic changes of subchondral bone seen in OA, such as osteophytosis and sclerosis. Amid a cohort of inflammatory cytokines, endothelin-1 (ET-1) could stimulate the osteoblast-mediated bone formation in both physiological (postnatal growth of trabecular bone) and pathological conditions (bone metastasis of prostate or breast cancer). Also, ET-1 is known as a mitogen and contributes to fibrosis in various organs, e.g., skin, liver, lung, kidney heart and etc., as a result of inflammatory or metabolic disorders. Subchondral bone sclerosis shared the similarity with fibrosis in terms of the overproduction of collagen type I. We postulated that ET-1 might have a hand in the subchondral bone sclerosis of OA. Meanwhile, ET-1 was also able to stimulate the production of matrix metalloproteinase (MMP)-1 and 13 by articular chondrocytes and synoviocytes, by which it might trigger the enzymatic degradation of articular cartilage. Taken together, ET-1 signaling may play a role in destruction of bone-cartilage unit in the pathogenesis of OA; it warrants further investigations to potentiate ET-1 as a novel diagnostic biomarker and therapeutic target for rescue of OA.
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong; Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sin
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong. Electronic address: paulwen@hku.hk.
authors.forename: C Y
authors.initials: CY
authors.lastname: Wen
authors.affiliation: Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong; Heart, Brain, Hormone and Healthy Aging Center, The University of Hong Kong, Pokfulam, Hong Kong; State Key Laboratory for Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: S K
authors.initials: SK
authors.lastname: Chung
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: K Y
authors.initials: KY
authors.lastname: Chiu
mesh_terms: D016723:Bone Remodeling / Q000502:physiology; D002356:Cartilage / Q000503:physiopathology*; D019902:Chondrocytes / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000502:physiology; D053509:Matrix Metalloproteinase 13 / Q000502:physiology; D010003:Osteoarthritis / Q000209:etiology* / Q000503:physiopathology*; D010012:Osteogenesis / Q000502:physiology*; D012598:Sclerosis / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1
keywords: Endothelin-1; Osteoarthritis; Subchondral bone