Soluble RANKL exaggerates hindlimb suspension‐induced osteopenia but not muscle protein balance
| العنوان: | Soluble RANKL exaggerates hindlimb suspension‐induced osteopenia but not muscle protein balance |
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| المؤلفون: | Toni L. Speacht, Charles H. Lang, Henry J. Donahue |
| المصدر: | J Orthop Res |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, musculoskeletal diseases, medicine.medical_specialty, 0206 medical engineering, Protein metabolism, Muscle Proteins, P70-S6 Kinase 1, 02 engineering and technology, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Cortical Bone, medicine, Animals, Orthopedics and Sports Medicine, Femur, Receptor, 030203 arthritis & rheumatology, biology, RANK Ligand, medicine.disease, 020601 biomedical engineering, Mice, Inbred C57BL, Osteopenia, Bone Diseases, Metabolic, Endocrinology, medicine.anatomical_structure, Hindlimb Suspension, chemistry, RANKL, Sarcopenia, biology.protein, Cortical bone |
| الوصف: | We examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor kappa-B ligand (RANKL) also exaggeratesgastrocnemius and quadriceps muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received 3 intraperitoneal injections of either human recombinant soluble RANKL or PBS as control (n=10/group) at 24 hour intervals starting on Day 1 of HLS. GC + RANKL and HLS mice exhibited similar decreases in trabecular bone volume and density in both proximal tibias and distal femurs. However, RANKL affected trabecular number, separation, and connectivity density, while HLS decreased trabecular thickness. The combination of RANKL and HLS exacerbated these changes. Similarly,GC + RANKL and HLS mice saw comparable decreases in cortical bone volume, thickness, and strength in femur midshafts, and combination treatment exacerbated these changes. Plasma concentrations of P1NP were increased in both groups receiving RANKL, while CTX concentrations were unchanged.HLS decreased gastrocnemius weight and was associated with a reduction in global protein synthesis, and no change in proteasome activity. This change was correlated with a decrease in S6K1 and S6 phosphorylation, but no change in 4E-BP1 phosphorylation. Injection of RANKL did not alter gastrocnemius or quadriceps muscle protein metabolism in GC or HLS mice.Our results suggest that injection of soluble RANKL exacerbates unloading-induced bone loss, but not unloading-induced gastrocnemius or quadriceps muscle loss. This article is protected by copyright. All rights reserved. |
| تدمد: | 1554-527X 0736-0266 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5fef418517c765dbe0ed99d77e02d64fTest https://doi.org/10.1002/jor.24917Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5fef418517c765dbe0ed99d77e02d64f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1554527X 07360266 |
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