Leptin modulates both resorption and formation while preventing disuse-induced bone loss in tail-suspended female rats
| Autor: | Aline Martin, Raphaël De Vittoris, Christian Alexandre, Ricardo C. Moraes, Martine Begeot, Laurence Vico, Marie-Hélène Lafage-Proust, Thierry Thomas, Valentin David |
|---|---|
| Přispěvatelé: | Communications Cellulaires et Différenciation (CCD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2005 |
| Předmět: |
musculoskeletal diseases
Leptin Tail medicine.medical_specialty [SDV]Life Sciences [q-bio] Adipokine Polymerase Chain Reaction Bone remodeling Weight-Bearing Endocrinology Osteoprotegerin Osteoclast Internal medicine medicine Animals [INFO]Computer Science [cs] Bone Resorption DNA Primers Bone mineral Bone Development biology Base Sequence Chemistry Reverse Transcriptase Polymerase Chain Reaction Resorption Rats medicine.anatomical_structure RANKL biology.protein RAT Female Corticosterone |
| Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2005, 146 (8), pp.3652-3659 |
| ISSN: | 0013-7227 |
| Popis: | In vitro studies have demonstrated leptin-positive effects on the osteoblast lineage and negative effects on osteoclastogenesis. Therefore, we tested the hypothesis that leptin may prevent tail-suspension-induced bone loss characterized by an uncoupling pattern of bone remodeling, through both mechanisms. Female rats were randomly tail-suspended or not and treated either with ip administration of leptin or vehicle for 3, 7, and 14 d. As measured by dual energy x-ray absorptiometry, tail-suspension induced a progressive decrease in tibia-metaphysis bone mineral density, which was prevented by leptin. Histomorphometry showed that this was related to the prevention of the transient increase in osteoclast number observed with suspension at d 7. These effects could be mediated by the receptor activator of nuclear factor κB-ligand (RANKL)/osteoprotegerin (OPG) pathway since we observed using direct RT-PCR, a suspension-induced increase in RANKL gene expression in proximal tibia at d 3, which was counterbalanced by leptin administration with a similar 3-fold increase in OPG expression and a RANKL to OPG ratio close to nonsuspended conditions. In addition, leptin prevented the decrease in bone formation rate induced by tail-suspension at d 14. The latter could be related to the role of leptin in mediating the reciprocal differentiation between adipocytes and osteoblasts, because leptin concurrently blunted the disuse-induced increase in bone marrow adipogenesis. In summary, these data suggest that peripheral administration of leptin could prevent disuse-induced bone loss through, first, a major inhibitory effect on bone resorption and, second, a delayed effect preventing the decrease in bone formation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|