• 생약학회지
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• 제40권2호
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• pp.83-88
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• 2009

Bone is continuously remodeled by osteoblasts and osteoclasts. Osteoclasts play an important role in bone metabolism by resorbing the bone matrix. Thus, the compounds inhibiting osteoclasts can improve bone diseases such as osteoporosis. The methanol extracts of 159 herbal medicines were screened for the inhibitory activity against differentiation of osteoclasts. Among the tested extracts, Achuranthis Radix and Corydalis Tuber showed relatively strong inhibitory activity against differentiation of osteoclasts, whereas they have no significant effect on proliferation of osteoclasts.

• International Journal of Oral Biology
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• 제45권3호
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• pp.92-98
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• 2020

Periodontitis is a bacteria-induced inflammatory disease associated with alveolar bone loss. Osteoclast is a macrophage-lineage cell that exhibits phagocytic activity; however, osteoclast phagocytic activity has not been demonstrated under pathological conditions. Diabetes is a pathological condition that exacerbates alveolar bone loss via periodontitis; therefore, we examined phagocytic osteoclasts in diabetic rats that had periodontitis. The rats were divided into the control (C), periodontitis (P), and diabetes with periodontitis (DP) groups. Diabetes and periodontitis were induced by streptozotocin injection and ligature of the mandibular first molars, respectively. On days 3 and 20 after the ligature, the rats were sacrificed, and osteoclasts containing inclusions were quantified by tartrate-resistant acid phosphatase staining. On day 3, there were more osteoclasts containing inclusions in the DP group than in the C group. Among inclusions, osteocyte-like cells and dense bodies were more frequently observed in the DP group than in the C group. Cytoplasm-like structures were elevated more in the DP group than in the C and P groups. However, no differences were observed on day 20. Interestingly, some osteoclasts were in contact with the osteocytes within the exposed lacunae and contained several inclusions within a large vacuole. Thus, the elevation of phagocytic osteoclasts in rats with diabetes and periodontitis provides insight into the role of osteoclast phagocytic activity under pathological conditions.

• Journal of Korean Dental Science
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• 제8권2호
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• pp.74-81
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• 2015

Purpose: In osteoclast differentiation, actin-rich membrane protrusions play a crucial role in cell adhesion. Odontogenic ameloblast-associated protein (Odam) contributes to cell adhesion by inducing actin rearrangement. Odam-mediated RhoA activity may play a significant role in multinucleation of osteoclasts. However, the precise function of Odam in osteoclast cell adhesion and differentiation remains largely unknown. Here, we identify a critical role for Odam in inducing osteoclast adhesion and differentiation. Materials and Methods: The expression of Odam in osteoclasts was evaluated by immunohistochemistry. Primary mouse bone marrow and RAW264.7 cells were used to test the cell adhesion and actin ring formation induced by Odam. Result: Odam was expressed in osteoclasts around alveolar bone. Odam transfection induced actin filament rearrangement and cell adhesion compared with the control or collagen groups. Overexpression of Odam promoted actin stress fiber remodeling and cell adhesion, resulting in increased osteoclast fusion. Conclusion: These results suggest that Odam expression in primary mouse osteoclasts and RAW264.7 cells promotes their adhesion, resulting in the induction of osteoclast differentiation.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.91-102
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• 2006

Objectives : Ulmus davidiana Planch (UD) has long been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions. Methods : This study was undertaken to address whether the water extract of the bark of UD could modulate proliferation of mouse osteoclasts in vitro and to investigate its effect on cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandin E2 (PGE2) and is highly expressed in osteoclasts. Mouse osteoclasts were tested in vitro for growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and expression after treatment with UD extract. Results : Its effects were compared with those of indomethacin (a nonselective COX inhibitor) and celecoxib (a selective COX-2 inhibitor) by Cell viability assay, Cell cycle analysis, Immunohistochemical analysis of PCNA expression, Western blot analysis and PGE2 Enzyme immunoassay (EIA). UD demonstrated a strong growth inhibitory action in both tested osteoclasts cells. The IC50s were $10\;{\mu}g/ml$ for UD, $6\;{\mu}M$ for celecoxib and $42\;{\mu}M$ for indomethacin. UD, as well as celecoxib and indomethacin, suppressed proliferation cell nuclear antigen expression and PGE2 synthesis in osteoclasts. UD inhibited COX-2 expression, whereas celecoxib inhibited COX-2 activity directly. Conclusion : UD selectively and effectively inhibits osteoclasts cell growth in vitro. Inhibitory action of PGE2 synthesis via suppression of COX-2 expression may be responsible for its anti-inflammatory activity.

• Journal of Dental Anesthesia and Pain Medicine
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• 제18권6호
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• pp.349-359
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• 2018

Background: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to ${\alpha}$-tocopherol. It has been reported that ${\alpha}$-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs). Methods: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol ($0-50{\mu}M$) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion. Results: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP. Conclusion: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.

• 대한소아치과학회지
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• 제35권4호
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• pp.597-606
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• 2008

본 연구는 TNFR family인 CD137 및 RANK, 파골세포의 CD137L와 T 세포의 RANKL 간의 역신호에 의한 이들 세포 의 역할을 알아보고자 하였다. 이에 RANKL 및 CD137L 자극으로 유도되는 역신호 전달에 의한 T 세포 활성과 파골세포분 화에 미치는 영향을 규명하고자 웅성 생쥐의 골수세포와 T 세포를 공동배양하여 다음과 같은 결과를 얻었다. 1. 생쥐 단핵세포주 및 골수유도 단핵전구세포에서 CD137L이 발현되며, CD137L 단클론 항체로 자극을 주었을 경우 파 골세포 표지단백질인 TRAP 양성 파골세포의 형성이 억제되었다. 2. 활성화된 $CD4^+$ 및 $CD8^+$ T 세포에서 RANKL을 발현하였으며 RANKL의 유사 수용체인 OPG 재조합 단백질을 처리 하여 $CD4^+$ 및 $CD8^+$ T 세포의 세포증식이 억제되었다. 이 연구의 결과는 CD137 자극에 의한 T 세포활성 및 RANK 자극에 의한 파골세포분화 및 활성이 각각 수용체에 결합하 는 라이겐드의 역신호에 의해 억제되었는데, 이는 파골세포와 T 세포의 과도한 활성을 제어하는 생체의 항상성조절에 관여하 는 기전으로 생각된다.

• 치위생과학회지
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• 제15권3호
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• pp.295-300
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• 2015

치주염을 유발한 쥐 치아의 근심면에서 상아질파괴세포와 뼈파괴세포의 형성을 비교하였다. 뼈파괴세포는 치주염 유발 후 3일까지 증가한 후 감소하였으나 상아질파괴세포는 치주염 유발 10일까지 서서히 증가하였으며 치주염 유발 전과 후의 상아질파괴세포의 수는 뼈파괴세포보다 적었다. 또한 치근 흡수는 상아질파괴세포가 증가함에 따라 증가하였다. 이들 결과는 치주염 시 상아질파괴세포 형성도 뼈파괴세포처럼 증가하나 뼈파괴세포보다 서서히 약하게 진행됨을 시사한다. 본 연구에서 사용한 동물 모델과 연구 결과는 치주염에서 상아질파괴세포와 뼈파괴세포의 형성이 차이가 있음을 제시하는 최초 보고이며, 이들 세포의 형성 기전의 차이를 규명하는 앞으로의 연구에 유용한 자료로 이용될 수 있을 것으로 판단한다.

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

• 대한치과교정학회지
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• 제34권6호
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• pp.506-513
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• 2004

본 연구는 하치조신경의 수술적 절단이 치주인대공간에서의 파골세포에 미치는 영향을 평가하기 위하여 시행하였다. 이를 위하여 실험동물을 젊은 쥐 군 과 성 쥐 군으로 구분하여 좌측 하악골에는 하치조신경절단을 시행하여 실험측으로, 우측하악골은 가수술측으로 사용하였다. Bundle 골 표면에 위치한 파골세포의 수 그리고 파골세포의 골 흡수 활성도를 조직 형태적으로 측정하였다. 또한 Substance P 면역반응 신경섬유의 분포 변화를 치주인대와 치 수조직에서 평가하였다. Substance P 면역반응 신경섬유는 양군 실험측에서 고갈됨으로서 하치조신경의 수술적 절단이 성공적이었다는 것을 확인 할 수 있었다 실험측에서 파골세포의 수가 젊은 쥐 군 과 성 쥐 군 모두에서 유의하게 감소하였다(p<0.01과 p<0.05). 그러나 파골세포의 골 흡수 활성도는 양군 모두에서 실험측과 가수술측 사이에 차이를 나타내지 않았다(P>0.05). 성 쥐 군에서 파골세포의 수가 젊은 쥐 군에 비해 유의하게 감소되었으며 (p<0.01), 파골세포의 골 흡수 활성도에서는 변화가 없었다(p>0.05). 이들 결과를 통하여 감각신경인 하치조신경의 절단과 연령증가는 치주인대 공간에서 Bundle골 표면의 파골세포의 수를 감소시켰으며 골 흡수 활성도에는 영향을 주지 않는 것으로 나타났다.

• BMB Reports
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• 제53권9호
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• pp.472-477
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• 2020

Osteoclasts are hematopoietic-derived cells that resorb bone. They are required to maintain proper bone homeostasis and skeletal strength. Although osteoclast differentiation depends on receptor activator of NF-κB ligand (RANKL) stimulation, additional molecules further contribute to osteoclast maturation. Here, we demonstrate that protocadherin-7 (Pcdh7) regulates formation of multinucleated osteoclasts and contributes to maintenance of bone homeostasis. We found that Pcdh7 expression is induced by RANKL stimulation, and that RNAi-mediated knockdown of Pcdh7 resulted in impaired formation of osteoclasts. We generated Pcdh7-deficient mice and found increased bone mass due to decreased bone resorption but without any defect in bone formation. Using an in vitro culture system, it was revealed that formation of multinucleated osteoclasts is impaired in Pcdh7-deficient cultures, while no apparent defects were observed in differentiation and function of Pcdh7-deficient osteoblasts. Taken together, these results reveal an osteoclast cell-intrinsic role for Pcdh7 in maintaining bone homeostasis.