Elucidation of pathophysiological mechanism of chronic obstructive pulmonary disease (COPD)-related osteoporosis
Project/Area Number |
19K18513
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | University of Occupational and Environmental Health, Japan |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 慢性閉塞肺疾患 / COPD / 骨粗鬆症 / サルコペニア / モデル動物 / 酸化ストレス / p38 MAPK / ミトコンドリア / 慢性閉塞性肺疾患 / 骨折 / 抗酸化防御機構 / Nrf2 / 骨形態計測 / 動物モデル / 身体活動性 / 骨形成能低下 / 海綿骨量減少 / COPD急性増悪 / 転倒 / 肺気腫 / 筋萎縮 / ロコモティブシンドローム |
Outline of Research at the Start |
慢性閉塞性肺疾患(COPD)は、骨粗鬆症やサルコペニアの危険因子とされているが、その病態は不明な点が多い。本研究では、我々が独自に確立させたCOPDに伴う筋骨格系疾患のモデル動物を用いて、COPDが筋や骨に与える影響因子を解明していく。本研究成果により、COPDに伴う筋骨格系疾患の病態が明らかになれば、病態に応じた治療を検討することが可能となり、ヒトにおいても有益な情報となることが予想される。
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Outline of Final Research Achievements |
To elucidate the molecular mechanism of osteoporosis associated with chronic obstructive pulmonary disease (COPD), we conducted investigations using an animal model. In COPD mice, despite no decrease in physical activity, musculoskeletal disorders (trabecular bone loss, impaired bone formation, soleus muscle weight loss, each muscle fiber atrophy, type I muscle fiber to type II muscle fiber switching) occurred, and oxidative stress markers were elevated in vivo. Focusing on p38 MAPK signaling pathway, the oxidative stress-related muscle atrophy signaling pathway, administration of antioxidants or p38 inhibitors prevented skeletal muscle disorder observed in COPD mice. Because of the close relationship between sarcopenia and osteoporosis, the results of our study may be the key to unraveling the molecular mechanism of COPD-associated osteoporosis.
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Academic Significance and Societal Importance of the Research Achievements |
改正高年齢者雇用安定法により勤労者は65歳まで継続して働くことが可能となり、高年齢の勤労者における健康寿命の維持・増進は今後の重要なテーマであると言える。慢性閉塞性肺疾患(COPD)は男性骨粗鬆症の主な原因であるが、COPD骨粗鬆症の病態メカニズムは未だ明らかではない。COPD骨粗鬆症の病態機序を解明していくことで、COPDを有する勤労者の健康寿命の維持・増進に貢献できるのではないかと考え、本研究を立案した。近年、勤労者の転倒災害が問題となっており、勤労者における転倒や骨折リスクを軽減させることで、労働力の維持・向上に繋がることが期待され、本研究成果による社会への波及効果は高いと考える。
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Report
(5 results)
Research Products
(53 results)
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[Journal Article] Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model2022
Author(s)
Mano Y, Tsukamoto M, Wang KY, Nabeshima T, Kosugi K, Tajima T, Yamanaka Y, Suzuki H, Kawasaki M, Nakamura E, Zhou Q, Azuma K, Nakashima T, Tamura Y, Kozaki K, Nakazato K, Li YS, Kawai K, Yatera K, Sakai A
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Journal Title
Journal of Bone and Mineral Metabolism
Volume: 40
Issue: 6
Pages: 927-939
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Bone microstructure changes due to once-/twice-weekly teriparatide administration: a report of five cases using high-resolution peripheral quantitative computed tomography2021
Author(s)
Tsukamoto M, Okimoto N, Mori M, Yoshioka T, Asano K, Ikejiri Y, Uzawa T, Yoshimura T, Suzuki H, Yamanaka Y, Kawasaki M, Sakai A
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Journal Title
Modern Rheumatology Case Reports
Volume: rxab048
Issue: 2
Pages: 1-4
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation2020
Author(s)
Manabu Tsukamoto, Toshiharu Mori, Eiichiro Nakamura, Yasuaki Okada, Hokuto Fukuda, Yoshiaki Yamanaka, Ken Sabanai, Ke-Yong Wang, Takeshi Hanagiri, Satoshi Kuboi, Kazuhiro Yatera, Akinori Sakai
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Journal Title
Osteoporosis and Sarcopenia
Volume: 6
Issue: 4
Pages: 179-184
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle.2019
Author(s)
Tsukamoto M, Wang KY, Tasaki T, Murata Y, Okada Y, Yamanaka Y, Nakamura E, Yamada S, Izumi H, Zhou Q, Azuma K, Sasaguri Y, Kohno K, Sakai A
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Journal Title
Bone
Volume: 120
Pages: 75-84
DOI
Related Report
Peer Reviewed
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[Journal Article] Depletion of WNT10A Prevents Tumor Growth by Suppressing Microvessels and Collagen Expression.2018
Author(s)
Kumagai M, Guo X, Wang KY, Izumi H, Tsukamoto M, Nakashima T, Tasaki T, Kurose N, Uramoto H, Sasaguri Y,Kohno K, Yamada S.
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Journal Title
International Journal of Medical Sciences
Volume: 16
Issue: 3
Pages: 416-423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Findings to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle2020
Author(s)
Manabu Tsukamoto, Ke-Yong Wang, Takashi Tasaki, Yoichi Murata, Yasuaki Okada, Yoshiaki Yamanaka, Eiichiro Nakamura, Sohsuke Yamada, Hiroto Izumi, Qian Zhou, Kagaku Azuma, Yasuyuki Sasaguri, Kimitoshi Kohno, Akinori Sakai
Organizer
The American Society for Bone and Mineral Research 2020 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Association between endogenous oxidative stress and muscle atrophy in the elastase-induced pulmonary emphysema mouse model2020
Author(s)
Yosuke Mano, Manabu Tsukamoto, Ke-Yong Wang, Kenji Kosugi, Takafumi Tajima, Yoshiaki Yamanaka, Eiichiro Nakamura, Tamiji Nakashima, Qian Zhou, Kagaku Azuma, Yun-shan Li, Kazuaki Kawai, Kazuhiro Yatera, Akinori Sakai
Organizer
The American Society for Bone and Mineral Research 2020 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Systemic Bone loss, Impaired Osteogenic Activity and Type I Muscle Fiber Atrophy in Mice with Elastase-Induced Pulmonary Emphysema: Establishment of a COPD-Related Osteoporosis/Sarcopenia Mouse Model2019
Author(s)
Manabu Tsukamoto, Toshiharu Mori, Ke-Yong Wang, Yasuaki Okada, Hokuto Fukuda, Keisuke Naito, Yoshiaki Yamanaka, Ken Sabanai, Eiichiro Nakamura, Kazuhiro Yatera, Akinori Sakai
Organizer
The American Society for Bone and Mineral Research 2019 Annual Meeting
Related Report
Int'l Joint Research
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