• 제목/요약/키워드: bone resorption factor

검색결과 157건 처리시간 0.021초

Osteoclast-derived SLIT3 is a coupling factor linking bone resorption to bone formation

  • Koh, Jung-Min
    • BMB Reports
    • /
    • 제51권6호
    • /
    • pp.263-264
    • /
    • 2018
  • We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of ${\beta}-catenin$. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption. A small truncated recombinant SLIT3 protein increased bone mass in an osteopenic mouse model. These results suggest that SLIT3 is a novel therapeutic target in metabolic bone diseases.

Propofol promotes osteoclastic bone resorption by increasing DC-STAMP expression

  • Kim, Eun-Jung;Kim, Hyung Joon;Baik, Seong Wan;Kim, Kyung-Hoon;Ryu, Sie Jeong;Kim, Cheul-Hong;Shin, Sang-Wook
    • Journal of Dental Anesthesia and Pain Medicine
    • /
    • 제18권6호
    • /
    • pp.349-359
    • /
    • 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.

녹제초 추출물이 파골세포 분화 및 골 흡수에 미치는 영향 (Effects of Pyrola japonica Extracts on Osteoclast Differentiation and Bone Resorption)

  • 박정식;임형호
    • 한방재활의학과학회지
    • /
    • 제29권2호
    • /
    • pp.135-147
    • /
    • 2019
  • Objectives This study was performed to evaluate the effect of Pyrola japonica extract (NJ) and its principal constituent, homoarbutin (HA) on osteoclast differentiation and gene expression and bone resorption. The osteoclastogenesis and gene expression were determined in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated RAW264.7 cell. Methods In order to evaluate the effect of HA extracted from NJ on bone resorption, osteoclasts were used to be differentiated and formed by stimulating RAW264.7 cells with RANKL. Tartarate-resistant acid phosphatase (TRAP) (+) polynuclear osteoclast formation ability was evaluated, and differentiation control genes including cathepsin K, matrix metalloproteinases-9 (MMP-9), and TRAP in osteoclast differentiation were analyzed by real-time polymerase chain reaction (PCR). Immunoblotting was performed to measure the effect of mitogen-activated protein kinase (MAPK) factors on bone resorption, and the effect of osteoclasts on osteoclast differentiation was measured. Results Both NJ and high concentration of HA blocked RANKL-stimulated differentiation from RAW264.7 cell to TRAP-positive multinucleated cells. NJ reduced RANKL-induced expression of TRAP, cathepsin K. Both NJ and high concentration of HA inhibited RANKL-mediated expression of MMP-9, nuclear factor of activated T-cells, cytoplasmic 1, and cellular Jun-fos. NJ suppressed RANKL-stimulated expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor-alpha, and levels of interleukins. Both NJ and HA decreased bone resorption in osteoclast-induced bone pit formation model. Conclusions These results suggest that NJ and HA blocked bone resorption by decreasing RANKL-mediated osteoclastogenesis through down-regulation of genes for osteoclast differentiation.

파골세포에 대한 Transforming Growth Factor-$\beta$의 활성화 작용 (Transforming Growth Factor-Beta Stimulates Osteoclastic Bone Resorption in vitro)

  • 양대석;김일찬;고성희;유병제;남궁용;강신성;이창호
    • 한국동물학회지
    • /
    • 제39권3호
    • /
    • pp.317-324
    • /
    • 1996
  • 파골세포는 골조직을 분해하는 세포로 알려져 있다. 따라서, 파골세포 활성조절은 골조직의 성장과 재조합의 조절에 있어 매우 중요한 의미를 갖는다. 기관배양을 통해 파골세포의 활성을 조절하는 여러가지 인자들이 알려져 있다. 그 중에서 transforming growth factor-$\beta$ (TGF-$\beta$)는 골조직 대사에 중요한 영향을 미치는 것이 알려져 있고, 또한 골조직내에 다량 존재하고 있기 때문에, TGF-$\beta$의 파골세포에 대한 효과를 알아보는 것은 전체 파골작용의 조절기작을 알아보는데 있어 중요한 의미를 갖는다. 본 연구인들은 계배를 이용한 파골세포의 배양법을 개발하였고, 이를 파골세포 활성을 측정하는데 사용하였다. 이 방법을 통해, TGF-$\beta$1이 파골세포의 골분해 활성을 증가시킨다는 것을 알수 있었다. 또한, 이러한 활성작용은 TGF-$\beta$의 파골세포에 대한 직접적인 효과라기 보다는 다른 세포를 통한 간접적인 효과일 가능성이 높다는 사실을 알 수 있었다. TGF-$\beta$에 의한 파골세포의 활성화는 nordihydroguaiaretic acid에 의해 현저하게 저해된 반면, idomethacin에 의해서는 저해되지 않았다. 이러한 실험결과들은 TGF-$\beta$가 arachidonic acid의 lipoxygenase 유도체를 통해 파골세포의 영향을 미칠 가능성을 제시하고 있다.

  • PDF

The effect of fibroblast growth factor receptor inhibition on resistance exercise training-induced adaptation of bone and muscle quality in mice

  • Cho, Suhan;Lee, Hojun;Lee, Ho-Young;Kim, Sung Joon;Song, Wook
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제26권3호
    • /
    • pp.207-218
    • /
    • 2022
  • Aging in mammals, including humans, is accompanied by loss of bone and muscular function and mass, characterized by osteoporosis and sarcopenia. Although resistance exercise training (RET) is considered an effective intervention, its effect is blunted in some elderly individuals. Fibroblast growth factor (FGF) and its receptor, FGFR, can modulate bone and muscle quality during aging and physical performance. To elucidate this possibility, the FGFR inhibitor NVP-BGJ398 was administrated to C57BL/6n mice for 8 weeks with or without RET. Treatment with NVPBGJ398 decreased grip strength, muscular endurance, running capacity and bone quality in the mice. FGFR inhibition elevated bone resorption and relevant gene expression, indicating altered bone formation and resorption. RET attenuated tibial bone resorption, accompanied by changes in the expression of relevant genes. However, RET did not overcome the detrimental effect of NVP-BGJ398 on muscular function. Taken together, these findings provide evidence that FGFR signaling may have a potential role in the maintenance of physical performance and quality of bone and muscles.

Tumor Necrosis Factor-α가 골대사에 미치는 영향 (EFFECT OF TUMOR NECROSIS FACTOR-α ON THE BONE METABOLISM)

  • 김상섭;이수종
    • Restorative Dentistry and Endodontics
    • /
    • 제24권1호
    • /
    • pp.187-199
    • /
    • 1999
  • Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

  • PDF

Interleukin-10 이 $interleukin-1{\beta}$로 유도되는 골흡수에 미치는 효과 (EFFECT OF INTERLEUKIM-10 ON THE BONE RESORPTION INDUCED BY INTERLEUKIN-1B)

  • 유윤정;강윤선;이승일
    • Journal of Periodontal and Implant Science
    • /
    • 제24권2호
    • /
    • pp.321-339
    • /
    • 1994
  • The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

  • PDF

Piperlongumine suppressed osteoclastogenesis in RAW264.7 macrophages

  • Jin, Sun-Mi;Kang, Hae-Mi;Park, Dan-Bi;Yu, Su-Bin;Kim, In-Ryoung;Park, Bong-Soo
    • International Journal of Oral Biology
    • /
    • 제44권3호
    • /
    • pp.89-95
    • /
    • 2019
  • Piperlongumine (PL) is a natural product found in long pepper (Piper longum). The pharmacological effects of PL are well known, and it has been used for pain, hepatoprotection, and asthma in Oriental medicine. No studies have examined the effects of PL on bone tissue or bone-related diseases, including osteoporosis. The current study investigated for the first time the inhibitory effects of PL on osteoclast differentiation, bone resorption, and osteoclastogenesis-related factors in RAW264.7 macrophages stimulated by the receptor activator for nuclear factor-${\kappa}B$ ligand (RANKL). Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and osteoclast differentiation and bone resorption were confirmed by tartrate-resistant acid phosphatase (TRAP) staining and pit formation analysis. Osteoclast differentiation factors were confirmed by western blotting. PL exhibited toxicity in RAW264.7 macrophages, inhibiting osteoclast formation and bone resorption, in addition to inhibiting the expression of osteoclastogenesis-related factors, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Fos, and NFATc1, in RANKL-stimulated RAW264.7 macrophages. These findings suggest that PL is suitable for the treatment of osteoporosis, and it serves as a potential therapeutic agent for various bone diseases.

치자 추출물이 RANKL 유도 파골세포 형성 및 골 흡수에 미치는 영향 (Effects of Gardeniae Jasminoides on RANKL-induced Osteoclastogenesis and Bone Resorption)

  • 최유경;황귀서
    • 대한한방내과학회지
    • /
    • 제38권6호
    • /
    • pp.1035-1048
    • /
    • 2017
  • Objectives: This study was performed to investigate the effects of Gardenia jasminoides extract (GJ) on osteoclast differentiation and bone resorption in vitro. Methods: To investigate the effect of GJ on osteoclast differentiation, the mouse leukemic myeloid cell line RAW 264.7 was stimulated by RANKL (receptor activator of nuclear factor kB ligand). Osteoclast differentiation was measured by counting TRAP (+) MNC in the presence of RANKL. To elucidate the mechanism of the inhibitory effect of GJ on osteoclast differentiation, gene expression of TRAP, Cathepsin K, MMP-9, NFATc1, c-Fos, MITF, DC-STAMP, CTR, OC-STAMP and Atp6v0d2 was measured using reverse transcription-PCR (RT-PCR). Bone resorption was measured using the bone pit formation assay. Results: GJ decreased the number of TRAP (+) MNCs in the presence of RANKL. GJ inhibited the expression of cathepsin K, MMP-9, TRAP, MITF, NFATc1, c-Fos, iNON, OC-STAMP, Atp6v0d2, and DC-STAMP in the osteoclast, and inhibited bone pit formation in vitro. Conclusions: The results suggest that GJ has inhibitory effects on bone resorption resulting from inhibition of osteoclast differentiation and gene expression.

The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

  • Kim, Yu Li;Lee, Sun Kyoung;Park, Kwang-Kyun;Chung, Won-Yoon
    • Journal of Cancer Prevention
    • /
    • 제21권2호
    • /
    • pp.88-94
    • /
    • 2016
  • Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.