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Int J Mol Med. 2016 Aug;38(2):585-93. doi: 10.3892/ijmm.2016.2629. Epub 2016 Jun 8.

Increased RANKL expression in peripheral T cells is associated with decreased bone mineral density in patients with COPD.

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Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.


Receptor activator of nuclear factor-κB ligand (RANKL)-expressing adaptive T cells contribute to bone damage in autoimmune arthritis, although their role in chronic obstructive pulmonary disease (COPD)-associated osteoporosis is unknown. In the present study, the functional expression of RANKL in CD4+/CD8+ T cells and Th17 cells, and the potential role of these cells in COPD-associated bone loss was investigated. A total of 36 non-smokers, 38 smokers with normal lung function and 57 patients with COPD were enrolled. Femoral and vertebral bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RANKL expression in peripheral CD4+ and CD8+ T cells and Th17 cells was evaluated by flow cytometry. For in vitro experiments, CD4+ and CD8+ T cells from 17 non-smokers were evaluated for RANKL expression following dose-dependent culture with cigarette smoke extract (CSE) for 5 days. The frequencies of RANKL-positive CD4+ and CD8+ T cells were higher in the patients with COPD than in the non-smokers (P=0.001 and P=0.002, respectively). The proportion of CD4+ T cells positive for both RANKL and interleukin-17 (IL-17) was higher in the patients with COPD than in the non-smokers (P=0.010). However, the frequency of RANKL-expressing Th17 cells was similar among all groups (P=0.508). The frequency of RANKL+CD4+ T cells inversely correlated with BMD of the lumbar vertebrae (P=0.01, r=-0.229), and that of the femoral neck (P<0.001, r=-0.350). The results of our in vitro experiments revealed that CSE increased RANKL expression in CD4+ T cells only. The percentages of RANKL-positive CD4+ T cells and RANKL- and IL-17 double-positive CD4+ T cells were increased in the peripheral blood of patients with COPD, and the former were associated with BMD. These observations suggest that RANKL+CD4+ T cells may be mechanistically linked to diseases of the lung and bone in patients with COPD.

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