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3.6). It is now also apparent that the cell rests of Malassez have a number of important functions in normal periodontal homeostasis, including cementogenesis, healing and regeneration (Keinan and Cohen 2013 ; Xiong et al. 2013 ). They are thus important in maintaining periodontal health during all the normal challenges of tooth movement and function as well as in responses to trauma, orthodontic tooth movement, and periodontitis. These properties are being exploited in the development of therapeutic approaches to promote periodontal regeneration in the management of periodontal diseases (Xiong et al. 2013 ).
Table 3.2 Biological factors that have a role in the pathogenesis of radicular cyst.
| Factors | Cell(s) of origin | Target cell (ligand(s)) | Key function |
|---|---|---|---|
| Bacterial factors | |||
| LPS (endotoxin) | Bacteria | Fibroblasts and many cell types (CD14/TLR) | Induces a wide range of mediators, including CXCL8/IL‐8, TNF‐α, IL‐1, RANKL, OPG. Indirectly stimulates bone resorption |
| Cytokines | |||
| IL‐1α | Macrophages, PMN, osteoclasts, epithelial cells, dendritic cells | Attracts and activates PMNs; stimulates production of prostaglandins, proteolytic enzymes, cytokines IL‐6, IL‐8; stimulates bone resorption and inhibits bone formation (originally called osteoclast‐activating factor, OAF) | |
| IL‐1β | Macrophages | Monocytes | Inhibits osteoclast formation and bone resorption |
| IL‐6 | Macrophages, epithelial cells, PMN, Th2 cells, B lymphocytes, endothelial cells, fibroblasts | Activates and stimulates PMNs and T cells; stimulates differentiation of B lymphocytes into plasma cells; stimulates osteoclasts and bone resorption; down‐regulates production of IL‐1 | |
| TNF‐α | Macrophages, Th1 cells, PMN, fibroblasts | Activates lymphocytes and macrophages; stimulates bone resorption | |
| IL‐17 | Th17 | Up‐regulates secretion of IL‐1, IL‐6, TNF‐α, and IL‐8 secretion; attracts PMNs; stimulates osteoclasts and bone resorption | |
| GM‐CSF | Macrophages, T lymphocytes, endothelial cells, PMN | Functionally activates macrophages and PMNs | |
| TGF‐β | Lymphocytes (Treg), macrophages, fibroblasts, osteoblasts, osteoclasts, epithelial cells | PMNs, macrophages | Anti‐inflammatory; suppresses T and B lymphocytes; down‐regulates production of IL‐1, IL‐6, TNF‐α, and IFN‐γ; blocks production of nitric oxide by macrophages; inhibits bone resorption; inhibits Th17 and promotes Treg formation |
| IFN‐γ | Th1 cells, dendritic cells | Th lymphocytes | Activates macrophages; induces IL‐1 production; inhibits RANKL and bone resorption |
| IL‐12 | Th1 cells, macrophages, dendritic cells | Up‐regulates IL‐1 and IFN‐γ; stimulates Th1 differentiation; suppresses Th2 differentiation | |
| IL‐10 | Macrophages, dendritic cells, lymphocytes (Treg) | Anti‐inflammatory; down‐regulates IL‐1 and IFN‐γ; inhibits action of RANKL and bone resorption | |
| IL‐4 | Th2 cells | Inhibits bone resorption; inhibits Th17 formation; down‐regulates IL‐1 | |
| RANKL | Normally present on osteoblasts; also Th1cells, endothelial cells, fibroblasts, PMNs, epithelial cells; may be soluble | Osteoclasts and precursors (RANK) | Activates osteoclasts; positively regulates bone resorption |
| OPG | Osteoblasts, some epithelial cells, endothelial cells, B cells | Osteoblasts (RANKL) | Decoy receptor for RANKL and blocks RANK/RANKL pathway; inhibits osteoclastogenesis and negatively regulates bone resorption |
| Chemokines | |||
| CXCL8 (IL‐8) | Macrophages, PMN, Th1 cells, Th17 cells | CXCR1‐2 | Attracts PMNs and macrophages; chemotaxis and differentiation of osteoclasts |
| CXCL12 (SDF‐1α) | Endothelial cells | Osteoclast precursors (CXCR4); PMNs | Chemotaxis and differentiation of osteoclasts; attracts PMNs; up‐regulates MMPs |
| CCL7 (MCP‐3) | Endothelial cells, lymphocytes, fibroblasts, plasma cells | Osteoclasts and precursors | Chemotaxis and differentiation of osteoclasts |
| CCL5 (RANTES) | T cells, fibroblasts, osteoclasts, osteoblasts | Osteoclasts and precursors (CCR1, CCR5) | Chemotaxis and differentiation of osteoclasts |
| CCL‐2 (MCP‐1) | Osteoblasts | Osteoclasts and precursors (CCR2) | Chemotaxis and differentiation of osteoclasts |
| CCL3 (MIP‐1α) | Fibroblasts, osteoclasts, osteoblasts | Macrophages (CCR1), lymphocytes/Th1 (CCR5) | Chemotaxis and differentiation of osteoclasts; attracts macrophages |
| CCL4 (MIP‐1β) | Th1 cells | Chemotaxis and differentiation of osteoclasts; activates macrophages | |
| Prostaglandins | |||
| Prostaglandins (PGE2) | Macrophages, fibroblasts, inflammatory cells, epithelial cells, endothelial cells | Osteoclasts (receptors EP1–EP4) | Stimulates osteoclasts and bone resorption |
GM‐CSF,
