Regulation of Osteoclast Differentiation by Cytokine Networks

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.

Correlation between serum ODF and OCIF levels in lung cancer patients with bone metastasis / 中国肿瘤临床

Objective:This study was aimed to investigate the value of osteoclast differentiation factor (ODF) and osteoclastogen-esis inhibitory factor (OCIF) detection for clinical diagnosis and assessment of patient condition in bone metastasis of lung cancer. Methods:Data from 186 lung cancer patients who were preliminary diagnosed between July 2009 and April 2012 were analyzed. Cas-es were divided into the bone metastasis group with 82 cases (group A) and the non-bone metastasis group with 104 cases (group B). Concentrations of serum ODF and OCIF in each group were detected by ELISA. Results: ODF and OCIF values of group A were (32.22±6.22) ng/L and (41.23±8.13) ng/L, respectively, which were significantly higher than the corresponding values in group B [(8.35 ±5.42) ng/L and (10.15±4.42) ng/L]. The differences between the two groups were statistically significant (P0.05). Conclusion:The serum ODF and OCIF concentrations significantly increase when bone metastasis oc-curs in lung cancer patients. Hence, these variables are useful as indices for monitoring bone metastases and evaluating patient condi-tion. An extensive application prospect is proposed.

The influence of osteoclasts during the repairs of tooth root in rats model of tooth resorption by intermittent injection of parathyroid hormone (PTH) / 重庆医学

Objective To investigate the role of PT H (1-34 ) on the expression of receptor activator factor of NF-κB ligand (RANKL) in the induction of osteoclasts and its effect to osteoclasts on compression side during the repairs of tooth root in rats model of tooth resorption by intermittent injection of small dose of PTH (1-34) .Methods After the model of tooth resorption was established in rats 6-8 weeks in age ,63 male SD rats were divided in three groups .Rats in the control group were not given injec-tions for any drugs ;The negative control group were given injections for normal saline 6μg/kg subcutaneously every other day ;The experimental group were given injections for PTH (1-34) 6 μg/kg(PTH :1 μg/mL) subcutaneously every other day ;then rats in every group were killed on the day 0 ,7 ,10 ,14 ,17 ,21 ,25 .TRAP staining for counting TRAP-positive stained osteoclasts ,calculat-ing the mean ;Ligand RANKL immunohistochemistry and using image-pro-plus image analysis system to measure the average opti-cal density value of compression side .Results On the day of discontinuation ,the tooth resorption continued in each group ;the num-ber of osteoclasts between every two arrays there were no significant statistic differences (P>0 .05);RANKL immunohistochemis-try :Compared with control group and the negative control group ,the experimental group significantly increased in early stage ,and reduced in latest stage(P<0 .05) .Conclusion It indicated that intermittent injection of small dose PTH (1-34) did not cease the rats tooth resorption which occured during the period of tooth repair .

Effects of mechanical tensile stress on the expression of ODF mRNA in osteoblasts differentiated from rBMSCs in vitro / 医用生物力学

Objective To investigate the correlation between mechanical tensile stress and the expression of ODF mRNA in osteoblasts differentiated from rBMSCs, and elucidate the mechanism for osteoclastogenesis regulated by osteoblasts in bone modeling and remodeling during the process of orthodontic tooth movement. Method rBMSCs derived osteoblasts were isolated and cultured in vitro, and subjected to static mechanical tensile stress of 1, 3, 5 kPa or dynamic tensile stress of 3, 5 kPa at 0.017 Hz using the cellular tensile stress system for 24 h. The control groups were subjected without any strain. Cells were collected in 0, 3, 6, 9, 12, 24, 48 h respectively after stress loading. The expression patterns of ICAM-1 mRNA were examined by semiquantitative RT PCR assay. Results ODF mRNA level significantly decreased after dynamic tensile strain, compared with the control groups；the effects of inhibition did not positively correlated with the magnitude of strain; the expression of ODF mRNA gradually decreased at 6 h, significantly decreased at 9 h, then slightly rebounded and still stayed at a considerably lower level, reached the minimum transcription at 48 h. Conclusions The mechanical tensile strain can regulate osteoclastogenesis by inhibiting the expression of ODF in osteoblasts derived from rBMSCs. It could lead to a better understanding of the molecular basis for osteoblast osteoclast communication in bone resorption induced by the application of mechanical strain during the orthodontic tooth movement.

Expression of Osteoprotegerin and Osteoclast Differentiation Factor in Human Periodontal Ligament Fibroblast Cells / 대한치주과학회지

Recently, soluble TNF receptor homolog osteoprotegerin (OPG) and its membrane-bound ligand osteoclast differentiation factor (ODF) were found to regulate osteoclast formation and function, and bone metabolism. It is now well established that ODF acts via RANK expressed on hematopoietic osteoclast precursor cells to facilitate their differentiation to osteoclasts, and OPG prevents the formation of osteoclasts by interfering the binding of ODF and RANK. Expression of OPG and ODF was believed to be closely related to the pathogenesis of bone resorption and destruction from osteoporosis, periodontal diseases, malignant bone tumor, and arthritis. The periodontal ligament fibroblasts (PDLF), located between the tooth and tooth socket, has been thought to play an important role in maintaining bone homeostasis of periodontal tissues. However, the exact mechanism by which bone formation and resorption are regulated by PDLF is not well understood. In this study we have prepared primary cultures of human PDLF from periodontium of malaligned tooth extracted due to orthodontic reason, and determined steady state or inflammatory signal-induced OPG and ODF expression using RT-PCR and western blot analysis. OPG and ODF mRNA and protein were expressed constitutively in the PDLF and these expression were slightly increased by osteotropic cytokine IL-1beta. Lipopolysaccharide-treated PDLF showed decrease in OPG mRNA and protein expression, and increase in ODF mRNA and protein expression. These results indicated that PDLF influence the osteoclastogenesis by OPG and ODF expression in the inflammatory situation as well as physiological condition, and thereby pathogenesis of periodontal alveolar bone destruction.

Effects of strain force on the expression of osteoclast differentiation factor and osteoclasto-genesis inhibitory factor in human periodontal ligament cells / 实用口腔医学杂志

Objective:To investigate the effects of strain force on t he expression of osteoclast differentiation factor(ODF) and osteoclasto-genesis i nhibitory factor(OCIF) in human periodontal ligament cells (HPDLCs). Met hods: HPDLCs were subjected to cyclic strain force for 0, 6, 12 and 24 h ours, mRNA expression of ODF and OCIF were determined by RT-PCR. Result s:After treatment of the cells for 0,6,12 and 24 hours the ODF/?-actio n values were 0.7280?0.0261,0.6831?0.0411,0.5801?0.2230 and 0.4572?0.0373( P0.05) respectively.Conclusion:Strain force may decrease the expression of ODF and increase the expression of OCIF.

Regulating effect of 17?-estradiol on osteoprotegerin and osteoclast differentiation factor expressions in osteoblasts from newborn rats / 中华内分泌代谢杂志

Osteoblasts (OB) isolated from newborn SD rats were cultured in vitro.After treatment with different concentrations of 17?-estradiol (10~(-11)-10~(-6)mol/L),the mRNA expressions of osteoprotegerin (OPG) and osteoclast differentiation factor (ODF) in OB were measured by RT-PCR.17?-estradiol increased the expression of OPG in OB with the maximal effect at the concentration of 10~(-8) mol/L.No significant difference was observed in the expression of ODF in OB with different concentrations of 17?-estradiol.The therapeutic effect of estrogen on osteoporosis appears to be related to the enhanced OPG expression in OB at physiological concentration of estrogen.