The adipokine lipocalin-2 in the context of the osteoarthritic osteochondral junction

Corrigendum: The adipokine lipocalin-2 in the context of the osteoarthritic osteochondral junction. Scientific Reports, 6, 30666. https://doi.org/10.1038/srep30666Obesity 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-beta 1 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.The authors acknowledge Mr. Oliver Shaw for performing the English revision and the support of Dr. Esbrit's. The authors' research is supported by research grants from Fondo de Investigación Sanitaria funded by the Instituto de Salud Carlos III (PI12/00144, PI13/00570, CP15/00007, PI14/00016 and PIE13/00024). R.G. is funded by the Instituto de Salud Carlos III through a Miguel Servet programme. A.V. is the recipient of a fellowship from the Fundación Conchita Rábago. A.G.M. was funded by the Universidad Carlos III de Madrid (Spain). R.L. and O.G. were funded by the Instituto de Salud Carlos III. O.G. is a member of the RETICS Programme, RD12/0009/0008 Instituto de Salud Carlos III (ISCIII). The research is supported by research grant from FEDE

Oportunidades terapéuticas más allá del cartílago en la artrosis de rodilla: una perspectiva fisiopatológica

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Bioquímica y Biología Molecular I, leída el 06/11/2014Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Fac. de Ciencias BiológicasTRUEunpu

Compensatory anabolic signaling in the sarcopenia of experimental chronic arthritis

Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated alongside an increase in IL-1β, active NF-κB and a higher ratio of phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6 was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in myostatin from gastrocnemii and synovium with a congruent decrease in serum myostatin compared to controls. Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated IL-1β may trigger proteolysis via elevated NF-κB and p38 MAPK signaling with a compensatory anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular myostatinThis work was partially supported by research grants from the Instituto de Salud Carlos III (PI13/00570, PI15/00340, PI16/00065 and RETICEF RD12/0043/0008), co-funded by Fondo Europeo de Desarrollo Regional (FEDER) and ASPIRE IIR grant from Pfizer

Lipid Transport and Metabolism in Healthy and Osteoarthritic Cartilage

Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules to chondrocytes, determining cell metabolism and cartilage maintenance. Lipids are important nutrients in chondrocyte metabolism and are available for these cells through de novo synthesis but also through diffusion from surrounding tissues. Cartilage status and osteoarthritis development depend on lipid availability. This paper reviews lipid transport and metabolism in cartilage. We also analyze signalling pathways directly mediated by lipids and those that involve mTOR pathways, both in normal and osteoarthritic cartilage

Corrigendum: Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis.

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Dietary fats and osteoarthritis: insights, evidences, and new horizons

Osteoarthritis (OA) is a progressive, age-related disease characterized by the degradation of the cartilage, abnormal bone remodeling, and joint pain eventually leading to disability. The occurrence of clinically diagnosed OA and the incidence of disability show geographic variations, which suggests that lifestyle and factors such as diet play a vital role in the formation and progression of OA. Obesity is associated with a state of low-grade inflammation and increased plasma concentrations of fatty acids such as the saturated fatty acids (SFA). Importantly, obesity is a major risk factor for the development of OA in both weight-bearing and non-weight-bearing joints. Further, obese individuals bear the full brunt of OA which poses a huge health, social and economic problem, and hence it is essential to increase our understanding of OA and obesity to improve patient care and decrease disease progression. Hence, the current state of knowledge on the relationship between obesity and OA is reviewed, especially the influence of different diets. In particular, we emphasize the role and mechanisms of SFA to cause or worsen O