Journal of bone and mineral metabolism · 2026
Gut microbiota transmits osteoimmune dysregulation and exacerbates trabecular bone loss in tristetraprolin-deficient mice.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kwack Kyu Hwan, Sohn Jiho, Zhang Lixia, Li Lu, Mullaney Reegan, Arao Yukitomo, Blackshear Perry J, Kirkwood Keith L
Аннотация
INTRODUCTION: Tristetraprolin (TTP) is an RNA-binding protein essential for controlling cytokine production, and its deficiency leads to profound skeletal deterioration. Although TTP deficiency is associated with systemic inflammation and microbial dysbiosis, the contribution of the gut microbiota to bone pathology remains poorly defined.
MATERIALS AND METHODS: We investigated whether the microbiome causally modulates osteoimmune mechanisms and bone microarchitecture in TTP-deficient mice. To isolate the effects of the microbiome, we utilized specific pathogen-free (SPF) and germ-free (GF) co-housing mouse models.
RESULTS: Microbial transfer bidirectionally regulated systemic inflammation and the expansion of monocytic myeloid-derived suppressor cells (M-MDSCs), a population with potent osteoclastogenic capacity. Importantly, microbiota transfer was sufficient to induce osteoclast activation and a selective deterioration of trabecular bone microarchitecture in otherwise healthy mice, without affecting overall bone mass. Crucially, the transmission of these osteoimmune and skeletal phenotypes was microbiota-dependent; while a baseline genetic bone deficit persisted in GF TTP-deficient mice, the co-housing-induced M-MDSC expansion and trabecular bone alterations were not observed under GF conditions.
CONCLUSION: Our findings identify a microbiota-dependent osteoimmune axis that amplifies inflammatory bone loss in TTP deficiency. This work establishes the gut microbiome as a mechanistic modifier of bone quality in genetically driven inflammatory disease and highlights microbial targeting as a potential therapeutic strategy for inflammatory bone loss.
MATERIALS AND METHODS: We investigated whether the microbiome causally modulates osteoimmune mechanisms and bone microarchitecture in TTP-deficient mice. To isolate the effects of the microbiome, we utilized specific pathogen-free (SPF) and germ-free (GF) co-housing mouse models.
RESULTS: Microbial transfer bidirectionally regulated systemic inflammation and the expansion of monocytic myeloid-derived suppressor cells (M-MDSCs), a population with potent osteoclastogenic capacity. Importantly, microbiota transfer was sufficient to induce osteoclast activation and a selective deterioration of trabecular bone microarchitecture in otherwise healthy mice, without affecting overall bone mass. Crucially, the transmission of these osteoimmune and skeletal phenotypes was microbiota-dependent; while a baseline genetic bone deficit persisted in GF TTP-deficient mice, the co-housing-induced M-MDSC expansion and trabecular bone alterations were not observed under GF conditions.
CONCLUSION: Our findings identify a microbiota-dependent osteoimmune axis that amplifies inflammatory bone loss in TTP deficiency. This work establishes the gut microbiome as a mechanistic modifier of bone quality in genetically driven inflammatory disease and highlights microbial targeting as a potential therapeutic strategy for inflammatory bone loss.