Exogenous parathyroid hormone attenuates ovariectomy-induced skeletal muscle weakness in vivo.
Bone
; 151: 116029, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34111645
ABSTRACT
Osteoporosis commonly affects the elderly and is associated with significant morbidity and mortality. Loss of bone mineral density induces muscle atrophy and increases fracture risk. However, muscle lipid content and droplet size are increased by aging and mobility impairments, inversely correlated with muscle function, and a cause of reduced motor function. Teriparatide, the synthetic form of human parathyroid hormone (PTH) 1-34, has been widely used to treat osteoporosis. Although PTH positively affects muscle differentiation in vitro, the precise function and mechanisms of muscle mass and power preservation are still poorly understood, especially in vivo. In this study, we investigated the effect of PTH on skeletal muscle atrophy and dysfunction using an ovariectomized murine model. Eight-week-old female C57BL/6J mice were ovariectomized or sham-operated. Within each surgical group, the mice were divided into PTH injection or control subgroups. Motor function was evaluated based on grip strength, treadmill running, and lactic acid concentration. PTH receptor was expressed in skeletal muscle cells and myoblasts. PTH inhibited ovariectomy-induced bone loss but not uterine atrophy or increased body weight; PTH not only abolished ovariectomy-induced reduction in grip strength and maximum running speed, but also significantly reduced the ovariectomy-induced increase in lactic acid concentration (compared with that observed in the vehicle control). PTH also abrogated the ovariectomy-induced reduction in the oxidative capacity of muscle fibers, their cross-sectional area, and intramyocellular lipid content, and induced cell proliferation, cell migration, and muscle differentiation, while reducing lipid secretion by C2C12 myoblasts via the Wnt/ß-catenin pathway. PTH significantly ameliorated muscle weakness and attenuated exercise-induced lactate levels in ovariectomized mice. Our in vitro study demonstrated that PTH/Wnt signaling regulated the proliferation, migration, and differentiation of myoblasts and also reduced lipid secretion in myoblasts. Thus, PTH could regulate several aspects of muscle function and physiology, and may represent a novel therapeutic strategy for patients with osteoporosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_endocrine_disorders
Asunto principal:
Hormona Paratiroidea
/
Densidad Ósea
Límite:
Aged
/
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Bone
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón