title: The adipokine lipocalin-2 in the context of the osteoarthritic osteochondral junction.
abstract: Obesity and osteoarthritis (OA) form a vicious circle in which obesity contributes to cartilage destruction in OA, and OA-associated sedentary behaviour promotes weight gain. Lipocalin-2 (LCN2), a novel adipokine with catabolic activities in OA joints, contributes to the obesity and OA pathologies and is associated with other OA risk factors. LCN2 is highly induced in osteoblasts in the absence of mechanical loading, but its role in osteoblast metabolism is unclear. Therefore, because osteochondral junctions play a major role in OA development, we investigated the expression and role of LCN2 in osteoblasts and chondrocytes in the OA osteochondral junction environment. Our results showed that LCN2 expression in human osteoblasts and chondrocytes decreased throughout osteoblast differentiation and was induced by catabolic and inflammatory factors; however, TGF-β1 and IGF-1 reversed this induction. LCN2 reduced osteoblast viability in the presence of iron and enhanced the activity of MMP-9 released by osteoblasts. Moreover, pre-stimulated human osteoblasts induced LCN2 expression in human chondrocytes, but the inverse was not observed. Thus, LCN2 is an important catabolic adipokine in osteoblast and chondrocyte metabolism that is regulated by differentiation, inflammation and catabolic and anabolic stimuli, and LCN2 expression in chondrocytes is regulated in a paracrine manner after osteoblast stimulation.
authors.affiliation: Bone and Joint Research Unit, IIS-Fundación Jiménez Díaz, UAM, Avda Reyes Católicos, Madrid, 28040, Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Villalvilla
authors.affiliation: Department of Bioengineering, Universidad Carlos III de Madrid, CIEMAT-CIBERER, IIS-Fundación Jiménez Díaz, Madrid, 28040, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: García-Martín
authors.affiliation: Bone and Joint Research Unit, IIS-Fundación Jiménez Díaz, UAM, Avda Reyes Católicos, Madrid, 28040, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Largo
authors.affiliation: Research Laboratory 9 (NEIRID LAB), Institute of Medical Research, SERGAS, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
authors.affiliation: Bone and Joint Research Unit, IIS-Fundación Jiménez Díaz, UAM, Avda Reyes Católicos, Madrid, 28040, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.affiliation: Musculoskeletal Pathology Laboratory, Institute IDIS, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Gómez
mesh_terms: D054392:Adipokines / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000071068:Lipocalin-2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D054392:Adipokines; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D020780:Matrix Metalloproteinase 9