Effects of elastase-induced emphysema on muscle and bone in mice

• Published in: PloS one Vol. 18; no. 6; p. e0287541
• Main Authors: Matsumura, Daichi, Kawao, Naoyuki, Okumoto, Katsumi, Ohira, Takashi, Mizukami, Yuya, Akagi, Masao, Kaji, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.06.2023; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Autophagy; Biodegradation; Biology and Life Sciences; Bone Density - physiology; Bone Diseases, Metabolic; Bone loss; Bone mineral density; Bones; Cancellous bone; Chronic obstructive pulmonary disease; Complications and side effects; Cortical bone; Density; Diabetes; Diagnosis; Elastase; Emphysema; Fractures; Grip strength; Growth factors; Laboratory animals; Lung diseases; Lung diseases, Obstructive; Lungs; Medicine and Health Sciences; Mice; mRNA; Muscle, Skeletal; Muscles; Musculoskeletal system; Myostatin; Myostatin - genetics; Nutrition; Obstructive lung disease; Older people; Osteoporosis; Pancreatic elastase; Pancreatic Elastase - adverse effects; Parameters; Phosphatase; Proteolysis; Pulmonary Disease, Chronic Obstructive - chemically induced; Pulmonary Emphysema - chemically induced; Regression analysis; Research and Analysis Methods; Sarcopenia; Skeletal muscle; Swine; Tomography; Trachea; Tumor necrosis factor-TNF; Type 2 diabetes; Japan; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0287541

Chronic obstructive pulmonary disease (COPD) causes sarcopenia and osteoporosis. However, the mechanisms underlying muscle and bone loss as well as the interactions between muscle and bone in the COPD state remain unclear. Therefore, we herein investigated the effects of the COPD state on muscle and bone in mice intratracheally administered porcine pancreatic elastase (PPE). The intratracheal administration of PPE to mice significantly reduced trabecular bone mineral density (BMD), trabecular bone volume, trabecular number, cortical BMD and cortical area. It also significantly decreased grip strength, but did not affect muscle mass or the expression of myogenic differentiation-, protein degradation- or autophagy-related genes in the soleus and gastrocnemius muscles. Among the myokines examined, myostatin mRNA levels in the soleus muscles were significantly elevated in mice treated with PPE, and negatively related to grip strength, but not bone parameters, in mice treated with or without 2 U PPE in simple regression analyses. Grip strength positively related to bone parameters in mice treated with or without PPE. In conclusion, we showed that a PPE model of COPD in mice exerts dominant effects on bone rather than skeletal muscles. Increased myostatin expression in the soleus muscles of mice in the COPD state may negatively relate to a reduction in grip strength, but not bone loss.