Bone quality deteriorates in elastase-induced emphysema mice — ASN Events
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Bone quality deteriorates in elastase-induced emphysema mice (#216)

Manabu Tsukamoto 1 , Takayuki Nabeshima 1 , Ke-Yong Wang 2 , Yosuke Mano 1 , Daisuke Arakawa 1 , Eiichiro Nakamura 1 , Ryosuke Ozasa 3 , Takayoshi Nakano 3 , Akinori Sakai 1
  1. Orthopaedic Surgery, University of Occupational and Environmental Health, Kitakyushu, FUKUOKA, Japan
  2. Shared-Use Research Center, University of Occupational and Environmental Health, Kitakyushu, FUKUOKA, Japan
  3. Division of Materials and Manufacturing Science, Graduate School of Engineering, The University of Osaka, Suita, OSAKA, Japan

Background: The mechanisms underlying musculoskeletal disorders associated with chronic obstructive pulmonary disease (COPD) remain unclear. Because multiple factors contribute to these disorders in patients with COPD, animal models are needed for basic research. We previously demonstrated that intratracheal elastase (PPE) induces emphysema in mice and causes trabecular bone loss with reduced bone formation. However, its effects on bone quality remain unknown. This study aimed to investigate the impact of pulmonary emphysema on bone quality.

Methods: Twelve-week-old male C57BL/6J mice received intratracheal saline (saline group) or PPE (PPE group). Every 4 weeks, food intake, water intake, urine volume, fecal output, and spontaneous activity were evaluated using a metabolic cage and EthoVision XT. At 24 weeks after administration, the mice were sacrificed. The lungs, femurs, and tibiae were harvested. Pulmonary emphysema was assessed by mean linear intercept (Lm) in lung sections. Bone microstructure and histomorphometry were evaluated by micro-CT and histological analyses. Bone quality was assessed by microbeam X-ray diffraction using the Rigaku R-AXIS Bone Quality System. Bone marrow cells were also collected for CAGE-seq analysis.

Results: No significant differences were observed between the two groups in food intake, water intake, urine volume, fecal output, or spontaneous activity at any time point. At 24 weeks, the PPE group showed significantly higher Lm values than the saline group, confirming pulmonary emphysema. In vivo micro-CT showed that the rate of change in trabecular BMD in the femur was significantly lower in the PPE group than in the saline group from 8 weeks onward. Bone histomorphometry and ex vivo micro-CT showed that BV/TV, Tb.Th, Tb.N, Ob.S/BS, and Ob.N/BS were significantly lower in the PPE group. In addition, preferential alignment of biological apatite crystallites in the femoral diaphysis was reduced in the PPE group despite no significant decrease in cortical BMD. CAGE-seq showed that most of the altered genes in the PPE group were related to mitochondrial function and oxidative stress.

Conclusions: PPE-induced pulmonary emphysema deteriorated bone quality in mice, as reflected by impaired bone microstructure and apatite orientation.