Amniotic membrane mesenchymal stem cells-based therapy improves Bmi-1-deficient mandible osteoporosis through...

Mandible osteoporosis with age is characterized by greater fragility and accompanied with abnormal oral function. Mesenchymal stem cell transplantation can ameliorate osteoporosis. Bmi-1 is a transcriptional repressor which is an important regulator of cell cycle, stem cells self-renewal, and cell senescence. Here, we use a new kind of membrane mesenchymal stem cells (MSCs), amniotic membrane mesenchymal stem cells (AMSCs), to explore therapeutic effects on Bmi-1-deficient caused mandible osteoporosis. Phenotypes of mandibles from 5-week-old Bmi-1-deficient mice with AMSCs-based therapy were compared with age-matched Bmi-1-deficient mandibles without AMSCs-based therapy and wild-type mice. Bmi-1-deficient mice without AMSCs-based therapy displayed mandible osteoporosis accompanied with the rising senescence-associated molecules and imbalance redox homeostasis. Results showed that the alveolar bone volume, cortical thickness, type I collagen and osteocalcin immunopositive areas, mRNA expression levels of alkaline phosphatase, superoxide dismutase, gluathione reductase, and protein expression level of Runx2 were all reduced significantly in Bmi-1^-/- mandibles. Protein levels of PPARγ, p16, p21, p53, and redox gene levels of Bnip3l, Cdo1, Duox1, and Duox2 were up-regulated in mandibles from vehicle-transplanted Bmi-1^-/- mice. Also, osteoclasts were activated in Bmi-1^-/- alveolar bone. Transplanted AMSCs migrated into mandibles and improved all the parameters in Bmi-1^-/- mandibles with AMSCs-based therapy. These findings indicate that AMSCs-based therapy could rescue mandible osteoporosis induced by Bmi-1 deficiency through stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Our findings implied that AMSCs-based therapy had preventative and therapeutic potential for mandible osteoporosis.