Autophagy markers are decreased in bone of osteoporotic patients: a monocentric comparative study

Author:

Trojani Marie-Charlotte12,Clavé Arnaud13,Bereder Isabelle4,Camuzard Olivier15,Bernard De Dompsure Régis6,Gonzalez Jean-François6,Trojani Christophe7,Santucci-Darmanin Sabine18,Carle Georges F18ORCID,Breuil Véronique12,Pierrefite-Carle Valérie19ORCID

Affiliation:

1. Université Côte d’Azur, Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), UMR E4320 TIRO-MATOs , 06107 Nice , France

2. Service de Rhumatologie, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur II , 06000 Nice , France

3. Service de Chirurgie Orthopédique, Clinique Saint Georges , 06105 Nice , France

4. Service de Gériatrie, Centre Hospitalier Universitaire de Nice, Hôpital de Cimiez , 06000 Nice , France

5. Service de Chirurgie Réparatrice, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur II , 06000 Nice , France

6. Service de Chirurgie Orthopédique, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur II , 06000 Nice , France

7. Service de Chirurgie Orthopédique, Clinique Kantys , 06004 Nice , France

8. CNRS , 75005 Paris , France

9. INSERM , 75013 Paris , France

Abstract

Abstract Background Osteoporosis (OP) is a pathology characterized by bone fragility affecting 30% of postmenopausal women, mainly due to estrogen deprivation and increased oxidative stress. An autophagy involvement is suspected in OP pathogenesis but a definitive proof in humans remains to be obtained. Methods Postmenopausal women hospitalized for femoral neck fracture (OP group) or total hip replacement (Control group) were enrolled using very strict exclusion criteria. Western blot was used to analyze autophagy level. Results The protein expression level of the autophagosome marker LC3-II was significantly decreased in bone of OP patients relative to the control group. In addition, the protein expression of the hormonally upregulated neu-associated kinase (HUNK), which is upregulated by female hormones and promotes autophagy, was also significantly reduced in bone of the OP group. Conclusions These results demonstrate for the first time that postmenopausal OP patients have a deficit in bone autophagy level and suggest that HUNK could be the factor linking estrogen loss and autophagy decline. Clinical trial registration number ClinicalTrials.gov Identifier: NCT03175874, 2/6/2017.

Funder

Société Française de Rhumatologie

Publisher

Oxford University Press (OUP)

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