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Probiotics protect against tenofovir‐induced mandibular bone loss in mice by rescuing mandible‐derived mesenchymal stem cell proliferation and osteogenic differentiation
Author(s) -
Liu Hao,
Gu Ranli,
Li Wei,
Xue Jing,
Cong Zhe,
Wei Qiang,
Zhou Yongsheng
Publication year - 2020
Publication title -
journal of oral rehabilitation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 93
eISSN - 1365-2842
pISSN - 0305-182X
DOI - 10.1111/joor.12840
Subject(s) - mesenchymal stem cell , mandible (arthropod mouthpart) , tenofovir , stem cell , cell growth , microbiology and biotechnology , chemistry , medicine , dentistry , biology , human immunodeficiency virus (hiv) , immunology , genus , botany , biochemistry
Background Tenofovir disoproxil fumarate (TDF), a primary antiretroviral agent used to treat AIDS, triggers systematic bone loss. However, the effect of TDF on osteopenia or osteoporosis in the jaw remains unclear. TDF‐induced bone loss in the jaw, if any, likely involves mandible‐derived mesenchymal stem cells (MMSCs), which play a key role in jawbone metabolism. Probiotics prevent long bone loss, and could prove efficacious in treating TDF‐induced mandibular bone loss. Objectives To determine whether TDF triggers mandibular bone loss, elucidate the underlying mechanisms, and study the effect of Lactobacillus rhamnosus GG (LGG) on TDF‐induced bone loss in the jaw. Methods Tenofovir disoproxil fumarate was administered orally daily and LGG semiweekly from eight weeks to the end of the study (LGG group) to male C57BL6/J mice. The mice were sacrificed, and body weight (BW) and serum Ca and P were measured. Mandibular histomorphometry was evaluated by micro‐CT. MMSCs and LGG culture supernatants were isolated, and MMSC proliferation and ALP production when treated with different concentrations of LGG supernatant and/or TDF were measured. Relative abundance of osteogenic markers was assessed by qPCR. Results Orally administered LGG protected against bone mass loss and deterioration of bone microarchitecture and increased serum P levels. The BW of the TDF group was highest among the study groups. TDF partially impaired osteogenesis and proliferation of MMSCs. LGG culture supernatant rescued MMSC osteogenesis and proliferation, and osteogenic gene expression. Conclusions Lactobacillus rhamnosus GG protected against tenofovir‐induced mandibular bone loss in mice by rescuing MMSC proliferation and osteogenesis.