The effects of 1α,25-dihydroxyvitamin D3 on alveolar repair and bone mass in adiponectin-deficient mice.

Abstract Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. However, no drugs can regenerate lung tissue in COPD patients, and differentiation-inducing drugs that can effectively treat damaged alveoli are needed. In addition, the presence of systemic comorbidities is also considered problematic. Our previous study revealed that a retinoic acid derivative improved emphysema in elastase-induced COPD model mice at a dose of 1.0 mg/kg, whereas 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) showed an emphysema-improving effect in the same model at 0.1 μg/kg. Elastase-induced COPD model mice do not exhibit a systemic disease state, so evaluation in a model that better reflects the human disease state is considered necessary. To solve this problem, we focused on the adiponectin-deficient mouse and examined the effects of 1,25(OH)2D3 on alveolar regeneration. Fifty-week-old adiponectin-deficient mice were treated with 1,25(OH)2D3 (0.1 μg/kg) twice a week, for 30 weeks. The effects of pulmonary administration on alveolar repair were evaluated according to the distance between alveolar walls (Lm values) and computed tomography (CT) parameters. Bone density was evaluated based on CT. The administration of 1,25(OH)2D3 was confirmed to show a significant therapeutic effect. The Lm values in the control and 1,25(OH)2D3-treated groups were 98 ± 4 μm and 63 ± 1 μm, respectively. However, on CT, the average CT value and % of low attenuation area showed no significant change. In adiponectin-deficient mice, the reduction of bone density (cortical, spongy, and total bone), which is a systemic symptom of COPD, was significantly suppressed by 1,25(OH)2D3 at 80 weeks of age. The present study suggests that 1,25(OH)2D3 could be a potential candidate drug that may provide a radical cure for the lung disease and comorbidities of COPD patients. This work can lead to the development drugs that may provide a radical cure for COPD.