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Bone Abstracts (2013) 1 PP253 | DOI: 10.1530/boneabs.1.PP253

INSERM UMR-606, Lariboisière Teaching Hospital, Paris, France.


Objective: Chondrolysis, chondrocyte apoptosis, and local inflammation are described to exacerbate osteoarthritis development. We therefore aimed to investigate the effect of adrenomedullin (ADM) and its truncated peptide (22–52ADM) on in vitro and in vivo models. Both have exhibited anti-apoptotic and anti-inflammatory properties in collagen-induced arthritis (CIA) in mice.

Methods: In normoxia or hypoxia (physiological condition), ADM and its receptor complex (CLR, RAMPs) expression was investigated in bovine articular chondrocytes (BAC) at the mRNA (RT-qPCR) and protein levels (EIA, immunolfluorescence). ADM and 22–52ADM anti-apoptotic effect was assessed on Fas-ligand (FasL)-mediated apoptosis using caspase-specific fluorogenic substrates. To assess the ADM anti-inflammatory effect on IL1β-stimulated chondrocytes, RT-qPCR analyses were performed to assess production of pro-inflammatory factors. Secondly, meniscectomized mice were injected i.p. three times a week during 8 weeks with PBS, ADM or 22–52ADM (1.2 μg/g). Joints were then prepared for histological analysis to quantify chondrocyte apoptosis (TUNEL) and cartilage degradation (Safranin-O).

Results: Using immunofluorescence, we have demonstrated CLR and RAMPs were more colocalized when chondrocytes were cultured in hypoxia, and especially in inflammatory environment. Coupled with AMPc measurements, those data suggest that the receptor is functional. Moreover, in such conditions, ADM secretion was significantly increased and exogenous ADM (10−6 M) demonstrated anti-apoptotic activity. Nevertheless, ADM failed to modulate mRNA production of pro-inflammatory factors. Regarding joint degradation rate of meniscetomized mice, neither ADM nor the 22–52ADM have had a protective effect on apoptosis and chondrolysis.

Conclusion: In «physiological environment», BAC were able to produce both ADM and functional receptor components. In addition, ADM treatment prevented FasL-induced apoptosis in hypoxia although its anti-inflammatory effect was not confirmed in these cells. Contrary to our expectations based on the CIA model, ADM or its derived peptide 22–52ADM administered systemically did not disclose any effect on OA progression. Direct intra-articular effects of ADM might be investigated.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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