Probiotics protect against tenofovir‐induced mandibular bone loss in mice by rescuing mandible‐derived mesenchymal stem cell proliferation and osteogenic differentiation

Abstract

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. 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. 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. 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. Lactobacillus rhamnosus GG protected against tenofovir-induced mandibular bone loss in mice by rescuing MMSC proliferation and osteogenesis.