• 제목/요약/키워드: osteoclasts

검색결과 309건 처리시간 0.027초

MicroRNA-26a Regulates RANKL-Induced Osteoclast Formation

  • Kim, Kabsun;Kim, Jung Ha;Kim, Inyoung;Lee, Jongwon;Seong, Semun;Park, Yong-Wook;Kim, Nacksung
    • Molecules and Cells
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    • 제38권1호
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    • pp.75-80
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    • 2015
  • Osteoclasts are unique cells responsible for the resorption of bone matrix. MicroRNAs (miRNAs) are involved in the regulation of a wide range of physiological processes. Here, we examined the role of miR-26a in RANKL-induced osteoclastogenesis. The expression of miR-26a was upregulated by RANKL at the late stage of osteoclastogenesis. Ectopic expression of an miR-26a mimic in osteoclast precursor cells attenuated osteoclast formation, actin-ring formation, and bone resorption by suppressing the expression of connective tissue growth factor/CCN family 2 (CTGF/CCN2), which can promote osteoclast formation via upregulation of dendritic cell-specific transmembrane protein (DC-STAMP). On the other hand, overexpression of miR-26a inhibitor enhanced RANKL-induced osteoclast formation and function as well as CTGF expression. In addition, the inhibitory effect of miR-26a on osteoclast formation and function was prevented by treatment with recombinant CTGF. Collectively, our results suggest that miR-26a modulates osteoclast formation and function through the regulation of CTGF.

Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway

  • Kim, Kabsun;Kim, Jung Ha;Kim, Inyoung;Seong, Semun;Kim, Nacksung
    • Molecules and Cells
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    • 제43권1호
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    • pp.34-47
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    • 2020
  • The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo. Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.

Combined effects of soy isoflavone and lecithin on bone loss in ovariectomized mice

  • Kim, Sang Baek;Assefa, Freshet;Lee, Su Jeong;Park, Eui Kyun;Kim, Sung Soo
    • Nutrition Research and Practice
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    • 제15권5호
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    • pp.541-554
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    • 2021
  • BACKGROUND/OBJECTIVES: Isoflavones (ISFs) are effective in preventing bone loss, but not effective enough to prevent osteoporosis. Mixtures of soy ISF and lecithin (LCT) were prepared and characterized in an attempt to improve the bone loss. MATERIALS/METHODS: The daidzein (DZ) and genistein (GN) solubility in soy ISF were measured using liquid chromatography-mass spectrometry. The change in the crystalline characteristics of soy ISF in LCT was evaluated using X-ray diffraction analysis. Pharmacokinetic studies were conducted to evaluate and compare ISF bioavailability. Animal studies with ovariectomized (OVX) mice were carried out to estimate the effects on bone loss. The Student's t-test was used to evaluate statistical significance. RESULTS: The solubility of DZ and GN in LCT was 125.6 and 9.7 mg/L, respectively, which were approximately 25 and 7 times higher, respectively, than those in water. The bioavailability determined by the area under the curve of DZ for the oral administration (400 mg/kg) of soy ISF alone and the soy ISF-LCT mixture was 13.19 and 16.09 ㎍·h/mL, respectively. The bone mineral density of OVX mice given soy ISF-LCT mixtures at ISF doses of 60 and 100 mg/kg daily was 0.189 ± 0.020 and 0.194 ± 0.010 g/mm3, respectively, whereas that of mice given 100 mg/kg soy ISF was 0.172 ± 0.028 g/mm3. The number of osteoclasts per bone perimeter was reduced by the simultaneous administration of soy ISF and LCT. CONCLUSIONS: The effect of preventing bone loss and osteoclast formation by ingesting soy ISF and LCT at the same time was superior to soy ISF alone as the bioavailability of ISF may have been improved by the emulsification and solvation of LCT. These results suggest the possibility of using the combination of soy ISF and LCT to prevent osteoporosis.

Remifentanil promotes osteoblastogenesis by upregulating Runx2/osterix expression in preosteoblastic C2C12 cells

  • Yoon, Ji-Young;Kim, Tae-Sung;Ahn, Ji-Hye;Yoon, Ji-Uk;Kim, Hyung-Joon;Kim, Eun-Jung
    • Journal of Dental Anesthesia and Pain Medicine
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    • 제19권2호
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    • pp.91-99
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    • 2019
  • Background: The imbalance between osteoblasts and osteoclasts can lead to pathological conditions such as osteoporosis. It has been reported that opioid adversely affect the skeletal system, but it is inconsistent. Remifentanil is currently used as an adjuvant analgesic drug in general anesthesia and sedation. The aim of the present study was to investigate the effect of remifentanil on the osteoblast differentiation and mechanism involved in this effect. Methods: The C2C12 cells (mouse pluripotent mesenchymal cell line) were used as preosteoblast. Osteoblastic differentiation potency was determined by alkaline phosphatase (ALP) staining. C2C12 cell migration by remifentanil was evaluated using Boyden chamber migration assay. The expression of Runx2 and osterix was evaluated by RT-PCT and western blot analysis to investigate the mechanism involved in remifentanil-mediated osteoblast differentiation. Results: ALP staining showed that remifentanil increased significantly osteoblast differentiation. In Boyden chamber migration assay, C2C12 cell migration was increased by remifentanil. RT-PCR and western blot analysis showed that the expression of Runx2 and osterix was upregulated by remifentanil. Conclusions: We demonstrated that remifentanil increased osteoblast differentiation in vitro by upregulation of Runx2 and osterix expression. Therefore, remifentanil has the potential for assisting with bone formation and bone healing.

Comparison of tooth movement and biological response in corticotomy and micro-osteoperforation in rabbits

  • Kim, Junghan;Kook, Yoon-Ah;Bayome, Mohamed;Park, Jae Hyun;Lee, Won;Choi, Hojae;Abbas, Noha H.
    • 대한치과교정학회지
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    • 제49권4호
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    • pp.205-213
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    • 2019
  • Objective: The aim of this study was to evaluate the amount of tooth movement and histologic changes with different corticotomy designs and micro-osteoperforation in rabbits. Methods: The sample consisted of 24 rabbits divided into three experimental groups (triangular corticotomy [TC] and indentation corticotomy [IC] with flap, and flapless micro-osteoperforations [MP]) and a control. A traction force of 100 cN was applied by connecting the first premolars to the incisors. The amount of tooth movement was measured. Kruskal-Wallis test was used to assess differences in tooth movement between the groups. Micro-computed tomography, hematoxylin and eosin staining, and tartrate-resistant acidic phosphatase (TRAP) analysis were performed. Analysis of variance was applied to assess differences in TRAP-positive osteoclast count between the groups. Results: The amount of tooth movement increased by 46.5% and 32.0% in the IC and MP groups, respectively, while the bone fraction analysis showed 69.7% and 8.5% less mineralization compared to the control. There were no significant intergroup differences in the number of TRAP-positive osteoclasts. Conclusions: The micro-osteoperforation group showed no significant differences in the amount of tooth movement compared to the corticotomy groups, nor in the TRAP-positive osteoclast count compared to both corticotomy groups and control.

Post-extraction pain in the adjacent tooth after surgical extraction of the mandibular third molar

  • Park, Won-Jong;Park, Il Kyung;Shin, Kyung Su;Choi, Eun Joo
    • Journal of Dental Anesthesia and Pain Medicine
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    • 제19권4호
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    • pp.201-208
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    • 2019
  • Background: After tooth extraction, pain due to dry socket and pain in the adjacent tooth are common. The aim of this study was to retrospectively analyze pain in the adjacent tooth after surgical extraction of the mandibular third molar. Methods: Postoperative pain due to dry socket, pain in the adjacent tooth, and pain from other causes were present. Group A included patents with dry socket alone; group B included patients with pain in the adjacent tooth alone; and group C included patients with both. The duration of symptoms was recorded. In addition, the prognosis of pain was divided into the complete improvement, improvement, maintenance, deterioration, and complete deterioration groups. Results: A total of 312 mandibular third molars were extracted from 13, 60, and 10 patients in groups A, B, and C, respectively. The mean duration of symptoms was 5 days in group A and B and 15.2 days in group C. There were statistically significant differences in the duration of symptoms between groups A and C and groups B and C. Conclusion: Pain in the adjacent tooth after third molar extraction can be caused by inflammatory reactions and pressure on this tooth. The pain caused by pressure on the periodontal ligament and alveolar bone results from the cytokines released by osteoclasts, which are responsible for bone destruction. However, pain from periodontal ligament damage caused by excessive pressure may be misunderstood as pulpal pain. Unconscious parafunctional habits, such as clenching and bruxism, could also be associated with post-extraction pain.

연교의 파골세포 분화 및 골 흡수 억제 기전 연구 (Forsythiae Fructus Extract Inhibits RANKL-Induced Osteoclast Differentiation and Prevent Bone Loss in OVX-Induced Osteoporosis Rat)

  • 엄지환;김재현;김민선;김상우;신화정;정혁상;손영주
    • Korean Journal of Acupuncture
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    • 제36권2호
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    • pp.115-126
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    • 2019
  • Objectives : Osteoporosis is a condition characterized by low bone mass and increased bone fragility. It has become a major problem of senior citizens. The purpose of this study is to experiment the effect of water extract of Forsythiae Fructus (wFF) on osteoclast differentiation; and the other purpose is to examine the effect of wFF on osteoporosis in ovariectomized rat. Methods : To investigate the effect of wFF on osteoclast differentiation and activity, RAW 264.7 cells were used. The number of TRAP positive cell, TRAP activity, pit area, mRNA expression of makers (RANK, TRAP, CA II, CTK, MMP-9, NFATc1, c-Fos), protein expression of makers (NFATc1, c-Fos) were investigated. For in vivo study, 40 female Sprague-Dawley (SD) rats were induced osteoporosis by ovariectomy (OVX) and then tested for anti-osteoporosis effect by administration of wFF. Results : wFF suppressed osteoclatogenesis, TRAP activity and pit area formation. Moreover, wFF decreased the expression of master differentiation factors (NFATc1, c-Fos) and also reduced the osteoclastogenesis-related markers (TRAP, CA II, CTK, MMP-9). These suggest that wFF inhibit osteoclasts differentiation and bone resorption. In the OVX rat model, wFF inhibited decreasing of BMD and trabecular area. Conclusions : Forsythiae Fructus should be effective for osteoporosis prevention and treatment.

2-O-digalloyl-1,3,4,6-tetra-O-galloyl-β-D-glucose isolated from Galla Rhois suppresses osteoclast differentiation and function by inhibiting NF-κB signaling

  • Ihn, Hye Jung;Kim, Tae Hoon;Kim, Kiryeong;Kim, Gi-Young;Jeon, You-Jin;Choi, Yung Hyun;Bae, Jong-Sup;Kim, Jung-Eun;Park, Eui Kyun
    • BMB Reports
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    • 제52권6호
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    • pp.409-414
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    • 2019
  • Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

방사선 육종 차조기와 백출 복합물이 조골세포와 파골세포의 활성에 미치는 영향 (Effects of Perilla frutescens var. crispa and Atractylodes macrocephala Koidzumi mixture on Osteoblast Differentiation and Osteoclast Formation)

  • 심부용;지중구
    • 한국응용과학기술학회지
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    • 제38권1호
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    • pp.168-177
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    • 2021
  • 본 연구는 방사선 육종 차조기와 백출 복합물의 조골세포 분화 활성 및 파골세포 형성 억제를 조사하였다. 차조기와 백출 복합물은 MG-63 세포에서 ALP 활성 및 arlizarin red 염색을 확인하였고 조골세포 형성의 영향은 RAW 264.7 세포에서 TRAP 활성과 TRAP 염색을 진행하였다. 세포 독성시험에서 차조기와 백출 복합물은 50 ㎍/㎖ 농도 이하에서 안전한 것으로 확인되었다. ALP 활성 및 골석회화 형성 능력은 대조군보다 활성이 낮았으나, 파골세포에서 TRAP 활성을 유의적으로 감소시켰으며, 효과적으로 TRAP(+) 다핵세포를 억제하였다. 따라서 차조기와 백출 복합물은 골 흡수 억제 활성을 향상시켜 뼈 관련 질환의 예방 및 치료에 효과적인 것으로 보여진다.

Effect of nicotine on orthodontic tooth movement and bone remodeling in rats

  • Lee, Sung-Hee;Cha, Jung-Yul;Choi, Sung-Hwan;Kim, Baek-il;Cha, Jae-Kook;Hwang, Chung-Ju
    • 대한치과교정학회지
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    • 제51권4호
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    • pp.282-292
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    • 2021
  • Objective: To quantitatively analyze the effect of nicotine on orthodontic tooth movement (OTM) and bone remodeling in rats using micro-computed tomography and tartrate-resistant acid phosphatase immunostaining. Methods: Thirty-nine adult male Sprague-Dawley rats were randomized into three groups: group A, 0.5 mL normal saline (n = 9, 3 per 3, 7, and 14 days); group B, 0.83 mg/kg nicotine (n = 15, 5 per 3, 7, and 14 days); and group C, 1.67 mg/kg nicotine (n = 15, 5 per 3, 7, and 14 days). Each animal received daily intraperitoneal injections of nicotine/saline from the day of insertion of identical 30-g orthodontic force delivery systems. A 5-mm nickel-titanium closed-coil spring was applied between the left maxillary first molar (M1) and the two splinted incisors. The rate of OTM and volumetric bone changes were measured using micro-computed tomography. Osteoclasts were counted on the mesial alveolar bone surface of the distobuccal root of M1. Six dependent outcome variables, including the intermolar distance, bone volume fraction, bone mineral density, trabecular thickness, trabecular volume, and osteoclast number, were summarized using simple descriptive statistics. Nonparametric Kruskal-Wallis tests were used to evaluate differences among groups at 3, 7, and 14 days of OTM. Results: All six dependent outcome variables showed no statistically significant among group-differences at 3, 7, and 14 days. Conclusions: The findings of this study suggest that nicotine does not affect OTM and bone remodeling, although fluctuations during the different stages of OTM in the nicotine groups should be elucidated in further prospective studies.