Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice

Abstract Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no s...

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Autores principales:	Leena Sapra, Hamid Y. Dar, Asha Bhardwaj, Amit Pandey, Surbhi Kumari, Zaffar Azam, Vishu Upmanyu, Aleena Anwar, Prashant Shukla, Pradyumna K. Mishra, Chaman Saini, Bhupendra Verma, Rupesh K. Srivastava
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f857ab477ada43debe31efe4c151b153
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spelling	oai:doaj.org-article:f857ab477ada43debe31efe4c151b1532021-12-02T10:49:10ZLactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice10.1038/s41598-020-80536-22045-2322https://doaj.org/article/f857ab477ada43debe31efe4c151b1532021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80536-2https://doaj.org/toc/2045-2322Abstract Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.Leena SapraHamid Y. DarAsha BhardwajAmit PandeySurbhi KumariZaffar AzamVishu UpmanyuAleena AnwarPrashant ShuklaPradyumna K. MishraChaman SainiBhupendra VermaRupesh K. SrivastavaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leena Sapra Hamid Y. Dar Asha Bhardwaj Amit Pandey Surbhi Kumari Zaffar Azam Vishu Upmanyu Aleena Anwar Prashant Shukla Pradyumna K. Mishra Chaman Saini Bhupendra Verma Rupesh K. Srivastava Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
description	Abstract Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.
format	article
author	Leena Sapra Hamid Y. Dar Asha Bhardwaj Amit Pandey Surbhi Kumari Zaffar Azam Vishu Upmanyu Aleena Anwar Prashant Shukla Pradyumna K. Mishra Chaman Saini Bhupendra Verma Rupesh K. Srivastava
author_facet	Leena Sapra Hamid Y. Dar Asha Bhardwaj Amit Pandey Surbhi Kumari Zaffar Azam Vishu Upmanyu Aleena Anwar Prashant Shukla Pradyumna K. Mishra Chaman Saini Bhupendra Verma Rupesh K. Srivastava
author_sort	Leena Sapra
title	Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
title_short	Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
title_full	Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
title_fullStr	Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
title_full_unstemmed	Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice
title_sort	lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing treg-th17 cell balance in ovx mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f857ab477ada43debe31efe4c151b153
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Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice

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