Bone remodeling involves the interplay of bone resorption and formation and is accurately controlled to maintain bone mass. Both processes require transcellular Ca ²⁺ transport, but the molecular mechanisms engaged remain largely elusive. The epithelial Ca ²⁺ channel TRPV5 is one of the most Ca ²⁺ -selective transient receptor potential (TRP) channels. In this study, the functional role of TRPV5 in bone was investigated. TRPV5 mRNA was expressed in human and murine bone samples and in osteoclasts along with other genes involved in transcellular Ca ²⁺ transport, including calbindin-D _9K and calbindin-D _28K , Na ⁺ /Ca ²⁺ exchanger 1, and plasma membrane Ca ²⁺ -ATPase 1b. TRPV5 expression in murine osteoclasts was confirmed by immunostaining and showed predominant localization to the ruffled border membrane. However, TRPV5 was absent in osteoblasts. Analyses of femoral bone sections from TRPV5 knockout (TRPV5 ^-/- ) mice revealed increased osteoclast numbers and osteoclast area, whereas the urinary bone resorption marker deoxypyridinoline was reduced compared with WT (TRPV5 ^+/+ ) mice. In an in vitro bone marrow culture system, the amount of osteoclasts and number of nuclei per osteoclast were significantly elevated in TRPV5 ^-/- compared with TRPV5 ^+/+ mice. However, using a functional resorption pit assay, we found that bone resorption was nearly absent in osteoclast cultures from TRPV5 ^-/- mice, supporting the impaired resorption observed in vivo . In conclusion, TRPV5 deficiency leads to an increase in osteoclast size and number, in which Ca ²⁺ resorption is nonfunctional. This report identifies TRPV5 as an epithelial Ca ²⁺ channel that is essential for osteoclastic bone resorption and demonstrates the significance of transcellular Ca ²⁺ transport in osteoclastic function.

Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. They are a heterogeneous cell population with differences in size, phenotype, and function. Although monocytes maintain several tissue-specific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. Identification of a growing number of functionally different subsets of cells within populations of monocyte-derived immune cells has recently put monocyte heterogeneity into sharp focus. Here, we summarize recent findings in monocyte heterogeneity and their differentiation into dendritic cells, macrophages, and osteoclasts. We also discuss these advances in the context of the formation of functionally different monocyte-derived subsets of dendritic cells, macrophages, and osteoclasts.

Disequilibrium between bone‐forming osteoblasts and bone‐resorbing osteoclasts is central to many bone diseases. Here, we show that dysregulated expression of translationally controlled isoforms of CCAAT/enhancer‐binding protein β (C/EBPβ) differentially affect bone mass. Alternative translation initiation that is controlled by the mammalian target of rapamycin (mTOR) pathway generates long transactivating (LAP^*, LAP) and a short repressive (LIP) isoforms from a single C/EBPβ transcript. Rapamycin, an inhibitor of mTOR signalling increases the ratio of LAP over LIP and inhibits osteoclastogenesis in wild type (WT) but not in C/EBPβ null (c/ebpβ^−/−) or in LIP knock‐in (L/L) osteoclast precursors. C/EBPβ mutant mouse strains exhibit increased bone resorption and attenuated expression of MafB, a negative regulator of osteoclastogenesis. Ectopic expression of LAP and LIP in monocytes differentially affect the MafB promoter activity, MafB gene expression and dramatically affect osteoclastogenesis. These data show that mTOR regulates osteoclast formation by modulating the C/EBPβ isoform ratio, which in turn affects osteoclastogenesis by regulating MafB expression.

Objective: To determine whether leukocyte‐platelet‐rich fibrin (L‐PRF) and advanced platelet‐rich fibrin (A‐PRF+) differ in their in vitro capacity to induce proliferation and migration of periodontal fibroblasts.Background: L‐PRF and A‐PRF + are autologous materials used in periodontal regenerative surgery. They derive from blood from patients, but have different characteristics. The literature is controversial regarding the effects of the two PRF preparations on periodontal tissue fibroblasts.Materials and methods: L‐PRF and A‐PRF + membranes were prepared from eight patients and incubated in 3 mL of culture medium for 2 days. Gingival fibroblasts (G‐F) and periodontal ligament fibroblast (PDL‐F) primary cells were retrieved from 7 donors. These cells were pre‐cultured for 1 day in wound healing experiment plates leaving a gap of 500 ± 50 µm in a concentration of 3.3 x 10⁵ cells/mL. 70 µL of the cell suspension was placed in each half of the well. Thereafter, the pre‐cultured L‐PRF and A‐PRF + supernatants were added to the experimental plates, and the fibroblasts were incubated for another 24 h. Medium alone (NEG) and fibroblast growth factor II (FGF) were used as controls. Subsequently, cell migration was registered for 24 h with live cell imaging in a time frame microscope at 5% CO₂ in air at 37°C. Images were analyzed using ImageJ. Cell proliferation and cell viability were measured.Results: L‐PRF and A‐PRF + induced higher cell proliferation than FGF and NEG. Both A‐PRF + and L‐PRF induced significant faster artificial wound closure than controls. Both PRF conditioned media induced faster cell migration in the initial phase (P < .01), but in the stoppage phase, the induced migration was higher for the A‐PRF+, compared with L‐PRF (P < .01).Conclusion: L‐PRF and A‐PRF + have a stimulatory effect on migration and proliferation of periodontal fibroblasts, and artificial wound closure was longer sustained by A‐PRF + than L‐PRF.