Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation
Abstract Background Cigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-02836-z |
| _version_ | 1831588201748234240 |
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| author | Yi Lu Yuanpu Peter Di Ming Chang Xin Huang Qiuyan Chen Ni Hong Beth A. Kahkonen Marissa E. Di Chunyan Yu Evan T. Keller Jian Zhang |
| author_facet | Yi Lu Yuanpu Peter Di Ming Chang Xin Huang Qiuyan Chen Ni Hong Beth A. Kahkonen Marissa E. Di Chunyan Yu Evan T. Keller Jian Zhang |
| author_sort | Yi Lu |
| collection | DOAJ |
| description | Abstract Background Cigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation. Methods We developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated. Results Smoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression. Conclusions Our findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a “smoke sensor” for bone remodeling. |
| first_indexed | 2024-12-17T22:08:33Z |
| format | Article |
| id | doaj.art-e47cfc0f9424458e860ae75bd682e2da |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-17T22:08:33Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e47cfc0f9424458e860ae75bd682e2da2022-12-21T21:30:47ZengBMCJournal of Translational Medicine1479-58762021-04-0119111610.1186/s12967-021-02836-zCigarette smoke-associated inflammation impairs bone remodeling through NFκB activationYi Lu0Yuanpu Peter Di1Ming Chang2Xin Huang3Qiuyan Chen4Ni Hong5Beth A. Kahkonen6Marissa E. Di7Chunyan Yu8Evan T. Keller9Jian Zhang10School of Medicine, Southern University of Science and TechnologyDepartment of Environmental and Occupational Health, University of PittsburghSchool of Medicine, Southern University of Science and TechnologySchool of Medicine, Southern University of Science and TechnologyState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer CenterSchool of Medicine, Southern University of Science and TechnologyDepartment of Environmental and Occupational Health, University of PittsburghDepartment of Environmental and Occupational Health, University of PittsburghDepartment of Urology & Pathology, University of MichiganDepartment of Urology & Pathology, University of MichiganSchool of Medicine, Southern University of Science and TechnologyAbstract Background Cigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation. Methods We developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated. Results Smoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression. Conclusions Our findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a “smoke sensor” for bone remodeling.https://doi.org/10.1186/s12967-021-02836-zCigarette smokingInflammationBone remodelingNFκB |
| spellingShingle | Yi Lu Yuanpu Peter Di Ming Chang Xin Huang Qiuyan Chen Ni Hong Beth A. Kahkonen Marissa E. Di Chunyan Yu Evan T. Keller Jian Zhang Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation Journal of Translational Medicine Cigarette smoking Inflammation Bone remodeling NFκB |
| title | Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation |
| title_full | Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation |
| title_fullStr | Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation |
| title_full_unstemmed | Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation |
| title_short | Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation |
| title_sort | cigarette smoke associated inflammation impairs bone remodeling through nfκb activation |
| topic | Cigarette smoking Inflammation Bone remodeling NFκB |
| url | https://doi.org/10.1186/s12967-021-02836-z |
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