• 동의생리병리학회지
• /
• 제22권6호
• /
• pp.1566-1571
• /
• 2008

Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI stainingrevealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권1호
• /
• pp.65-71
• /
• 2013

The transient receptor potential melastatin type 7 (TRPM7) channel is a widely expressed non-selective cation channel with fusion to the C-terminal alpha kinase domain and regarded as a key regulator of whole body $Mg^{2+}$ homeostasis in mammals. However, the roles of TRPM7 during osteoclastogenesis in RAW264.7 cells and bone marrow-derived monocyte/macrophage precursor cells (BMMs) are not clear. In the present study, we investigate the roles of TRPM7 in osteoclastogenesis using methods of small interfering RNA (siRNA), RT-PCR, patch-clamp, and calcium imaging. RANKL (receptor activator of NF-${\kappa}B$ ligand) stimulation did not affect the TRPM7 expression and TRPM7-mediated current was activated in HEK293, RAW264.7, and BMM cells by the regulation of $Mg^{2+}$. Knock-down of TRPM7 by siTRPM7 reduced intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increases by 0 mM $[Mg^{2+}]_e$ in HEK293 cells and inhibited the generation of RANKL-induced $Ca^{2+}$ oscillations in RAW264.7 cells. Finally, knock-down of TRPM7 suppressed RANKL-mediated osteoclastogenesis such as activation and translocation of NFATc1, formation of multinucleated cells, and the bone resorptive activity, sequentially. These results suggest that TRPM7 plays an essential role in the RANKL-induced $[Ca^{2+}]_i$ oscillations that triggers the late stages of osteoclastogenesis.

• Journal of Periodontal and Implant Science
• /
• 제38권sup2호
• /
• pp.395-404
• /
• 2008

Purpose: Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor (TNF) receptor family that inhibits bone resorption by suppressing osteoclastogenesis. Gingival fibroblasts (GF) play a role in periodontal disease progression, and the purpose of this experiment was to evaluate influence of osteotropic factors on the expression of osteoprotegerin mRNA in these cells. Materials and Methods: In this experiment, the influence of osteoclastogenic factors, interleukin-1 beta (IL-$1{\beta}$), TNF-$\alpha$, prostanglandin E2 ($PEG_2$). parathyroid hormone (PTH) and 1$\alpha$, 25-dihydroxyvitamin $D_3$ on the expression of osteoprotegerin mRNA in GF was studied by Northern blot hybridization. Results: As expected, $PEG_2$ tended to inhibit OPG levels and this was most prominent at 24 hours of culture with $10^{-7}M$ of $PEG_2$. TNF-$\alpha$ at 10ng/ml and also at 25ng/ml decreased OPG levels to almost 30% of the control at 24 hours. This contrasts with reports of increased OPG levels from osteoblast/stromal cells and gingival fibroblasts stimulated by TNF-$\alpha$. Decrease of OPG levels with $PEG_2$ and TNF-$\alpha$ suggests a pathway whereby these mediators exert their resorptive effects. However, OPG levels were increased almost 3-fold at 24 hours with IL-1$\beta$(1 to 15ng/ml) and increased 1.4 fold with 24-hour treatment of $10^{-7}M$ PTH. Conclusion: Increase of OPG levels suggests that these 'osteoclastogenic' factors act in more complex ways and may act to inhibit bone resorption in inflammatory periodontitis. This result supports the role of OPG as a negative feedback mechanism in osteoclastic activity.

• 대한치과교정학회지
• /
• 제24권4호
• /
• pp.871-883
• /
• 1994

This experiment was designed to study possible roles of $interleukin-1\beta$, interleukin-6 and tumor necrosis $factor-\alpha$ in bone remodeling by measuring their effects on $PGE_2,\; LTB_4$ and collagenase production when they were administered to human periodontal ligament fibroblasts. Human periodontal ligament fibroblasts were collected from first premolars extracted for orthodontic treatment. They were incubated in the environment of $37^{\circ}C,\;5\%\;Co^2,\;and\;100\%$ humidity. They were treated with $0.25\%$ trypsin-EDTA solution and centrifuged. PDL cells in the fifth to seventh passage were used for the experiment. Cells were seeded onto the culture dishes and when they were successfully attached, human recombinant $interleukin-1\beta$, interleukin-6, and tumor necrosis $factor-\alpha$ were administered, alone or in combination. They were incubated for 4, 8 and 24 hours and the levels of $PGE_2,\;LTB_4$ and collagenase released into the culture media were assessed by enzymeimmunoassay and collagenase activity assay. The conclusions are as follows: 1. $IL-1\beta\;and\;TNF-\alpha$ were very active in stimulating the production of $PGE_2$ and collagenase by human periodontal ligament fibroblasts, while IL-6 increased $LTB_4$ production. 2. $IL-1\beta$ significantly increased $PGE_2$, but $LTB_4$ Production was not increased. $IL-1\beta$ is thought to act mainly via the cyclooxygenase pathway of arachidonic acid metabolism. 3. IL-6 tended to inhibit $IL-1\beta$ in the production of $PGE_2$ and collagense whereas IL-6 and $TNF-\alpha$ showed auditive effect in the level of $PGE_2$. The above cytokines increased the release of at least one of $PGE_2,\;LTB_4$ and collagenase. It suggests that cytokines are involved in bone remodeling process by stimulating PDL fibroblasts to produce various bone-resorptive agents. The roles of cytokines in bone remodeling as a whole would need further study.

• Journal of Oral Medicine and Pain
• /
• 제38권1호
• /
• pp.87-95
• /
• 2013

측두하악관절 골관절염은 측두하악장애의 한 형태로 관절조직의 생리적 내성을 초과하는 기능적 부하가 지속적으로 관절에 가해졌을 때 관절연골 및 연골하 골조직의 점진적 파괴와 이차적 염증을 특징으로 하는 질환이다. 관절면에 가해지는 물리적 하중은 관절내에서 기질파괴 단백효소나 염증성 cytokine, 유리기의 활성을 증가시키고, 그에 따라 골조직의 퇴행과 재형성 사이의 균형을 깨뜨려 골조직의 흡수를 야기한다. 최근에는 물리적 하중 이 외에 비만세포에서 유래하는 adipokine이 골흡수를 증가시킨다는 보고들이 있으나 측두하악관절에 적용하기에는 아직 추가적인 연구가 필요하므로 현재로서 골관절염의 치료는 관절의 기능적 부하를 줄이고 환자의 생리적 내성을 증가시키는 방향으로 이루어져야 한다. 임상증상은 충분한 기간 정확한 술식대로 시행한 물리치료, 약물치료, 교합안정 장치치료 등의 보존적 처치와 관절강내 주사요법이나 관절세척술 및 관절경 수술과 같은 추가적인 외과적 처치에 의해 성공적으로 조절될 수 있으나, 임상증상의 개선이 골파괴의 중지와 재형성을 담보하는 것은 아니므로 임상증상의 개선 이 후에도 지속적인 골변화의 추적관찰이 필요하다. 또한, 골변화 활성 자체를 직접적으로 조절할 수 있는 활용 가능한 치료법이 없는 한, 지속적인 동기유발과 행동조절을 통해 관절에 가해지는 기능적 부하를 환자 스스로 조절할 수 있도록 끊임없이 교육하는 것이 골변화를 겪는 측두하악관절로 하여금 보다 이른 시기에 보다 유리한 정형적 안정에 도달하게 함으로써 골관절염을 보다 성공적으로 조절할 수 있는 길이라고 할 수 있다.