Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium

Abstract

BackgroundDyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model.MethodsLevels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression.ResultsApolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05).ConclusionThese findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia.

Intrinsic Features in MicroRNA Transcriptomes Link Porcine Visceral Rather than Subcutaneous Adipose Tissues to Metabolic Risk

“…For example, miR-10a-5p as a vital modulator, could suppress the growth of chronic myeloid leukemia CD34+ cells [39], and miR-10b-5p targets the potent inflammatory mediator KLF4 (Kruppel-like factor 4) [40] and has important roles in tumor invasion and the initiation of metastasis in breast cancer [41]. These results are consistent with the critical role of abdominal GOM in immune and inflammatory responses [19], [42], [43].…”

Expression of Toll‑like receptor 4 on mast cells in gingival tissues of human chronic periodontitis

“…TLR2 polymorphisms were found to be closely associated with aggressive periodontitis in a Japanese population (14). TLR2 and TLR4 were also shown to be important in mediating osteoclast differentiation of alveolar bone in response to dyslipidemia (15). In periodontitis, a previous study found that the expression of TLR4 was identified predominantly in connective tissues, and that no TLR4 was expressed in the relatively healthy gingival tissues of patients with periodontitis or in healthy gingival tissues, indicating that TLR4 was involved in the periodontitis immune response (16).…”

Two Neglected Biologic Risk Factors in Bone Grafting and Implantology: High Low-Density Lipoprotein Cholesterol and Low Serum Vitamin D

“…Furthermore, recent studies have pointed out possible links between periodontal infection and an increased risk for cardiovascular disease. 3,4 An increase of circulating levels of oxidized LDL induces alveolar bone loss 5,6 and is associated with the severity of the local inflammatory response to bacteria as well as the susceptibility to periodontal disease in diabetic patients. 7 Osteoblasts can bind, internalize, and then metabolize HDL3/LDL cholesterol and are capable of selectively taking up cholesteryl esters from these lipoproteins.…”