Irisin Protects against Loss of Trabecular Bone Mass and Strength in Adult Ovariectomized Mice by Stimulating Osteoblast Activity

Author:

Storlino Giuseppina1,Dicarlo Manuela2,Zerlotin Roberta2,Pignataro Patrizia23,Sanesi Lorenzo3,Suriano Clelia2,Oranger Angela2,Mori Giorgio1ORCID,Passeri Giovanni4ORCID,Colucci Silvia3,Grano Maria2ORCID,Colaianni Graziana2

Affiliation:

1. Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy

2. Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy

3. Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy

4. Unit of Clinica e Terapia Medica, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy

Abstract

Irisin is a peptide secreted by skeletal muscle that plays a major role in bone metabolism. Experiments in mouse models have shown that administration of recombinant irisin prevents disuse-induced bone loss. In this study, we aimed to evaluate the effects of irisin treatment for the prevention of bone loss in the ovariectomized (Ovx) mouse, the animal model commonly used to investigate osteoporosis caused by estrogen deficiency. Micro-Ct analysis conducted on Sham mice (Sham-veh) and Ovx mice treated with vehicle (Ovx-veh) or recombinant irisin (Ovx-irisn) showed bone volume fraction (BV/TV) decreases in femurs (Ovx-veh 1.39± 0.71 vs. Sham-veh 2.84 ± 1.23; p = 0.02) and tibia at both proximal condyles (Ovx-veh 1.97 ± 0.68 vs. Sham-veh 3.48 ± 1.26; p = 0.03) and the subchondral plate (Ovx-veh 6.33 ± 0.36 vs. Sham-veh 8.18 ± 0.41; p = 0.01), which were prevented by treatment with a weekly dose of irisin for 4 weeks. Moreover, histological analysis of trabecular bone showed that irisin increased the number of active osteoblasts per bone perimeter (Ovx-irisin 32.3 ± 3.9 vs. Ovx-veh 23.5 ± 3.6; p = 0.01), while decreasing osteoclasts (Ovx-irisin 7.6 ± 2.4 vs. Ovx-veh 12.9 ± 3.04; p = 0.05). The possible mechanism by which irisin enhances osteoblast activity in Ovx mice is upregulation of the transcription factor Atf4, one of the key markers of osteoblast differentiation, and osteoprotegerin, thereby inhibiting osteoclast formation.

Funder

Regione Puglia

CNR

University of Bari

European Space Agency

Next Generation EU

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference65 articles.

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