Dental pulp stem cells (DPSCs) have excellent proliferative properties, mineralization potential and can be easily obtained from third molar teeth. Recently, many studies have focused on isolation and differentiation of DPSCs. In our study, we focused on biological properties of non-differentiated DPSCs in comparison with osteogenic differentiated cells from DPSCs. We analyzed morphology as well as mineralization potential using three varied osteogenic differentiation media. After fifteen days of differentiation, calcium deposit production was observed in all three osteogenic differentiation media. However, only one osteogenic medium, without animal serum supplement, showed rapid and strong calcification—OsteoMAX-XF™ Differentiation Medium. Therefore, we examined specific surface markers, and gene and protein expression of cells differentiated in this osteogenic medium, and compared them to non-differentiated DPSCs. We proved a decrease in expression of CD9 and CD90 mesenchymal stem cell surface markers, as well as downregulation in the expression of pluripotency genes (NANOG and OCT-4) and increased levels of expression in osteogenic genes (ALP, BSP, OCN and RUNX2). Moreover, osteogenic proteins, such as BSP and OCN, were only produced in differentiated cells. Our findings confirm that carefully selected differentiation conditions for stem cells are essential for their translation into future clinical applications.

Background: External root resorption is an irreversible loss of dental hard tissue as a result of odontoclastic action. Multiple external cervical root resorptions in permanent teeth are rare. The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts. Case presentation: This case report demonstrates aggressive and generalized idiopathic external cervical root resorption that started and advanced during ongoing antiresorptive therapy with the human monoclonal RANKL-blocking antibody denosumab without discontinuation of therapy in a 74-year-old female patient treated for postmenopausal osteoporosis. The extent of resorptive defects was too large and progressively led to fractures of the teeth. The number of teeth involved and the extend of destruction excluded conservative treatment. The affected teeth had to be extracted for functional prosthetic reconstruction. Conclusions: This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.

Population aging has been a global trend for the last decades, which increases the pressure to develop new cell-based or drug-based therapies, including those that may cure bone diseases. To understand molecular processes that underlie bone development and turnover, we followed osteogenic differentiation of human dental pulp stem cells (DPSCs) using a specific induction medium. The differentiation process imitating in vivo osteogenesis is triggered by various signaling pathways and is associated with massive proteome and metabolome changes. Proteome was profiled by ultrahigh-performance liquid chromatography and comprehensively quantified by ion mobility-enhanced mass spectrometry. From 2667 reproducibly quantified and identified proteins, 432 were differentially abundant by strict statistic criteria. Metabolome profiling was carried out by nuclear magnetic resonance. From 27 detected metabolites, 8 were differentially accumulated. KEGG and MetaboAnalyst hinted metabolic pathways that may be involved in the osteogenic process. Enrichment analysis of differentially abundant proteins highlighted PPAR, FoxO, JAK-STAT, IL-17 signaling pathways, biosynthesis of thyroid hormones and steroids, mineral absorption, and fatty acid metabolism as processes with prominent impact on osteoinduction. In parallel, metabolomic data showed that aminoacyl-tRNA biosynthesis, as well as specific amino acids, likely promote osteodifferentiation. Targeted immunoassays validated and complemented omic results. Our data underlined the complexity of the osteogenic mechanism. Finally, we proposed promising targets for future validation in patient samples, a step toward the treatment of bone defects.

Therapeutic effects of arthrocentesis in treatment of temporomandibular joint disorders

Hyaluronic acid application vs arthroscopy in treatment of internal temporomandibular joint disorders