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.
Osteoclasts (OCLs) are key players in controlling bone remodeling. Modifications in their differentiation or bone resorbing activity are associated with a number of pathologies ranging from ...osteopetrosis to osteoporosis, chronic inflammation and cancer, that are all characterized by immunological alterations. Therefore, the 2000s were marked by the emergence of osteoimmunology and by a growing number of studies focused on the control of OCL differentiation and function by the immune system. At the same time, it was discovered that OCLs are much more than bone resorbing cells. As monocytic lineage-derived cells, they belong to a family of cells that displays a wide heterogeneity and plasticity and that is involved in phagocytosis and innate immune responses. However, while OCLs have been extensively studied for their bone resorption capacity, their implication as immune cells was neglected for a long time. In recent years, new evidence pointed out that OCLs play important roles in the modulation of immune responses toward immune suppression or inflammation. They unlocked their capacity to modulate T cell activation, to efficiently process and present antigens as well as their ability to activate T cell responses in an antigen-dependent manner. Moreover, similar to other monocytic lineage cells such as macrophages, monocytes and dendritic cells, OCLs display a phenotypic and functional plasticity participating to their anti-inflammatory or pro-inflammatory effect depending on their cell origin and environment. This review will address this novel vision of the OCL, not only as a phagocyte specialized in bone resorption, but also as innate immune cell participating in the control of immune responses.
The inflammatory diseases rheumatoid arthritis (RA) and periodontitis show similarities in misbalances of cytokine levels, such as tumor necrosis factor-α (TNF-α). RA has been treated for two decades ...with TNF inhibitors which are effective by blocking TNF's destructive action. Since RA and periodontitis show similarities in high levels of TNF, the periodontal status of RA patients may improve with the use of anti-TNF therapy. To assess this, a systematic review with special emphasis on duration of therapy was performed to evaluate the effect of anti-TNF-α treatment on the periodontal status of RA patients. Overall, studies showed an improvement in periodontal health with anti-TNF therapy. When analyzed over time (6 weeks to 9 months), it became apparent that initial improvements concerned bleeding on probing (BOP) and gingival index (GI) after therapy duration of 6 weeks. Periodontitis parameters that improved after prolonged treatment were: probing pocket depth (PPD) after 3 months and clinical attachment level (CAL) after 6 months. In conclusion, this systematic review reveals that anti-TNF treatment is therefore not only beneficial for rheumatic joints but also for the gums of rheumatoid arthritis patients. We propose that the sequential tissue recovery due to anti-TNF therapy progresses as follows: 1. block of diapedesis by lowering vessel permeability, 2 fewer leukocytes in the inflamed tissue, and 3. reduced proteolytic activity and subsequent repair of collagen fiber functionality and normalization of osteoclast activity. Clinically, this could lead to a decrease in bleeding on probing and ultimately in an improved clinical attachment level.
A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times ...higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.
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.
Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase ...(TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones--cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme cathepsin K, which was hardly expressed by FBGCs. Functionally, the latter cells were able to dissolve a biomimetic hydroxyapatite coating in vitro, which was blocked by inhibiting v-ATPase enzyme activity. These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts. However, they are not able to digest the matrix fraction of bone, likely due to the lack of a ruffled border and cathepsin K.
The oral pathogen Porphyromonas gingivalis is not only associated with periodontitis but also with systemic diseases elsewhere in the body. The mechanisms by which P. gingivalis travels from the oral ...cavity to other organs in the body are largely unknown. This review describes the four putative mechanisms supported by experimental evidence, which enable translocation of P. gingivalis over the oral mucosa, endothelial barriers and subsequent dissemination into the bloodstream.
The first mechanism: proteolytic enzymes secreted by P. gingivalis degrade adhesion molecules between tissue cells, and the extracellular matrix. This weakens the structural integrity of the mucosa and allows P. gingivalis to penetrate the tissue. The second is transcytosis: bacteria actively enter tissue cells and transfer to the next layer or the extracellular space. By travelling from cell to cell, P. gingivalis reaches deeper structures. Thirdly, professional phagocytes take up P. gingivalis and travel to the bloodstream where P. gingivalis is released. Lastly, P. gingivalis can adhere to the hyphae forming Candida albicans. These hyphae can penetrate the mucosal tissue, which may allow P. gingivalis to reach deeper structures.
More research could elucidate targets to inhibit P. gingivalis dissemination and prevent the onset of various systemic diseases.
Purpose of Review
Periodontitis is the inflammation-associated bone loss disease of the alveolar bone that surrounds teeth. Classically, the emphasis on the etiology of periodontitis has been on the ...products of periodontal pathogens that lead to an inflammatory response of the
soft
tissues of the periodontium, eventually leading to activation of osteoclasts that degrade the alveolar bone. Until recently, the response of osteocytes that populate the alveolar bone, and that are known for their regulatory role in bone anabolism and catabolism, has not been addressed.
Recent Findings
This review demonstrates that osteocytes play a key contributing role in periodontitis progression in various experimental mouse and rat periodontitis models. Osteocytes are the key expressing cells of both osteoclast differentiation factor RANKL as well as osteoblast activity regulator sclerostin. Targeted deletion of RANKL in osteocytes prevents osteoclast formation, thereby impairing periodontitis, despite the pressure of periodontitis-associated bacteria. Antibodies against the osteocyte-derived protein sclerostin inhibit and partially revert periodontitis by stimulating bone formation.
Summary
Experimental mouse and rat periodontitis models strongly indicate a key role for the bone-encapsulated osteocyte in understanding periodontitis etiology.