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Although functional association between Wnt signaling and bone homeostasis has been well described through genetic ablation of Wntless(Wls), the mechanisms of how osteoblastic Wlsregulates the fate of bone marrow stromal cells (BMSCs) and hematopoietic stem cells (HSCs) in relation to age are not yet understood. Here, we generated Col2.3‐Cre;Wlsfl/flmice that were free from premature lethality and investigated age‐related impacts of osteoblastic Wlsdeficiency on hematopoiesis, BM microenvironment, and maintenance of BMSCs (also known as BM‐derived mesenchymal stem/stromal cells) and HSCs. Ablation of osteoblastic Wlsdeteriorated BM microenvironment and bone mass accrual along with age‐independent effects on functions of BMSCs. Osteoblastic Wlsdeletion impaired HSC repopulation and progeny with skewing toward myeloid lineage cells only at old stage. As proven by hallmarks of stem cell senescence, osteoblastic Wlsablation differentially induced senescence of BMSCs and HSCs in relation to age without alteration in their BM frequency. Our findings support that deletion of Wlsin Col2.3‐expressing cells induces senescence of BMSCs and impairs BM microenvironment in age‐independent manner. Overall, long‐term deterioration in BM microenvironment contributes to age‐related HSC senescence with impaired progeny and hematopoiesis, which also suggests possible roles of osteoblastic Wlson the maintenance of BM HSCs. We investigated age‐related impacts of osteoblastic Wlsdeficiency on bone marrow (BM) and on the functions of BM‐conserved stem cells. Wlsdeletion in Col2.3‐expressing cells induces oxidative stress and senescence of bone marrow stromal cells (BMSCs) and impairs BM microenvironment and bone mass accrual in age‐independent manner. However, this ablation causes senescence of hematopoietic stem cells (HSCs) and deteriorates hematopoietic progenitor cell progeny and hematopoietic development only at old age.

Background: Mini-screws are widely used as temporary anchorages in orthodontic treatment, but have the disadvantage of showing a high failure rate of about 10%. Therefore, orthodontic mini-screws should have high biocompatibility and retention. Previous studies have demonstrated that the retention of mini-screws can be improved by imparting bioactivity to the surface. The method for imparting bioactivity proposed in this paper is to sequentially perform anodization, periodic pre-calcification, and heat treatments with a Ti–6Al–4V ELI alloy mini-screw. Materials and methods: A TiO2nanotube-structured layer was formed on the surface of the Ti–6Al–4V ELI alloy mini-screw through anodization in which a voltage of 20 V was applied to a glycerol solution containing 20 wt% H2O and 1.4 wt% NH4F for 60 min. Fine granular calcium phosphate precipitates of HA and octacalcium phosphate were generated as clusters on the surface through the cyclic pre-calcification and heat treatments. The cyclic pre-calcification treatment is a process of immersion in a 0.05 M NaH2PO4solution and a saturated Ca(OH)2solution at 90 °C for 1 min each. Results: It was confirmed that the densely structured protrusions were precipitated, and Ca and P concentrations, which bind and concentrate endogenous bone morphogenetic proteins, increased on the surface after simulated body fluid (SBF) immersion test. In addition, the removal torque of the mini-screw fixed into rabbit tibias for 4 weeks was measured to be 8.70 ± 2.60 N cm. Conclusions: A noteworthy point in this paper is that the Ca and P concentrations, which provide a scaffold suitable for endogenous bone formation, further increased over time after SBF immersion of the APH group specimens. The other point is that our mini-screws have a significantly higher removal torque compared to untreated mini-screws. These results represent that the mini-screw proposed in this paper can be used as a mini-screw for orthodontics.

Background:Periodontal ligament fibroblasts (PLFs) maintain homeostasis of periodontal ligaments by producing paracrine factors that affect various functions of stem‐like cells. It is hypothesized that PLFs induce proliferation and differentiation of stem cells more effectively than gingival fibroblasts (GFs) and skin fibroblasts (SFs). Methods:PLFs and GFs were isolated from extracted teeth and cultured in the presence and absence of osteogenesis‐inducing factors. Mouse embryonic stem (mES) cells and SFs were purchased commercially. mES cells were incubated with culture supernatants of these fibroblasts or cocultured directly with the cells. Proliferation and mineralization in mES cells were determined at various times of incubation. Immunostaining and polymerase chain reaction were performed. The activity of mitogen‐activated protein kinase and alkaline phosphatase (ALP) was also measured. Results:In cocultures, PLFs stimulated proliferation of mES cells more effectively than GFs or SFs. Similarly, the addition of culture supernatant of PLFs induced the most prominent proliferation of mES cells, and this was significantly inhibited by treatment with antibody against fibroblast growth factor (FGF)4 or the c‐Jun N‐terminal kinase inhibitor SP600125 (anthra[1,9‐cd]pyrazol‐6(2H)‐one). Supplementation with culture supernatant from the fibroblasts induced osteogenic differentiation of mES cells in the order PLFs > GFs > SFs. These activities of PLFs were related to their potential to produce osteogenic markers, such as ALP and runt‐related transcription factor‐2 (Runx2), and to secrete FGF7. Pretreatment of mES cells with the extracellular signal‐regulated kinase inhibitor PD98059 [2‐(2‐amino‐3‐methyoxyphenyl)‐4H‐1‐benzopyran‐4‐one] or SP600125 clearly attenuated mineralization induced by culture supernatant of PLF with attendant decreases in mRNA levels of Runx2, bone sialoprotein, osteocalcin, and osteopontin. Conclusion:PLFs regulate the proliferation and osteogenic differentiation of mES cells more strongly than GFs and SFs via the secretion of FGF through a mechanism that involves mitogen‐activated protein kinase‐mediated signaling.

Scaffolds combined with bioactive agents can enhance bone regeneration at therapeutic sites. We explore whether combined supplementation with coumaric acid and recombinant human-cartilage oligomeric matrix protein-angiopoietin 1 (rhCOMP-Ang1) is an ideal approach for bone tissue engineering. We developed coumaric acid-conjugated absorbable collagen scaffold (CA-ACS) and investigated whether implanting CA-ACS in combination with rhCOMP-Ang1 facilitates ACS- or CA-ACS-mediated bone formation using a rat model of critically sized mandible defects. We examined the mechanisms by which coumaric acid and rhCOMP-Ang1 regulate behaviors of human periodontal ligament fibroblasts (hPLFs). The CA-ACS exhibits greater anti-degradation and mechanical strength properties than does ACS alone. Implanting CA-ACS loaded with rhCOMP-Ang1 greatly enhances bone regeneration at the defect via the activation of angiogenic, osteogenic, and anti-osteoclastic responses compared with other rat groups implanted with an ACS alone or CA-ACS. Treatment with both rhCOMP-Ang1 and coumaric acid increases proliferation, mineralization, and migration of cultured hPLFs via activation of the Ang1/Tie2 signaling axis at a greater rate than treatment with either of them alone. Collectively, this study demonstrates that CA-ACS impregnated with rhCOMP-Ang1 enhances bone regeneration at therapeutic sites, and this enhancement is associated with a synergistic interaction between rhCOMP-Ang1-mediated angiogenesis and coumaric acid–related antioxidant responses.