Menú Cerrar

Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation

Yi Lu # 1 2Yuanpu Peter Di # 3Ming Chang # 1Xin Huang 1Qiuyan Chen 4Ni Hong 1Beth A Kahkonen 5Marissa E Di 5Chunyan Yu 6Evan T Keller 6Jian Zhang 7 8 9

J Transl Med. 2021 Apr 21;19(1):163.doi: 10.1186/s12967-021-02836-z.

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.