• Title/Summary/Keyword: Osteolysis

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Inhibitory Effect of Biotransformed-Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand

  • Park, Bobae;Yu, Sun Nyoung;Kim, Sang-Hun;Lee, Junwon;Choi, Sung Jong;Chang, Jeong Hyun;Yang, Eun Ju;Kim, Kwang-Youn;Ahn, Soon-Cheol
    • Journal of Microbiology and Biotechnology
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    • v.32 no.8
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    • pp.1017-1025
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    • 2022
  • Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

Treatment Outcome of Langerhans Cell Histocytosis (랑게르한스 세포 조직구증의 치료 결과)

  • Chung, So Hak;Kim, Jae Do;Jo, Hyun Ik
    • The Journal of the Korean bone and joint tumor society
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    • v.20 no.1
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    • pp.14-21
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    • 2014
  • Purpose: To analyze the clinical features and treatment outcome of Langerhans' cell histocytosis. Materials and Methods: From August 1996 to June 2013, 28 patients who histologically proven with LCH were analyzed of medical records, radiography, pathologic character retrospectively. Results: A total of 28 cases of LCH including 22 child has been reported. Onset age was 0.6 to 51 years old, occurred in the average age was 14.8 years. Follow-up period was 6 months to 134 months average was 44.6 months. The M:F ratio was 2.5:1. The initial symptoms was pain in 18 cases, 5 cases of pathologic fracture, 3 case of palpable mass, 1 case of discovered by accident in radiography, 1 case of torticollis. In radiological examination osteolysis was seen all cases, 7 cases showed a periosteal reaction, 1 case showed soft tissue extension. Clinical type of all cases were eosinophilic granuloma. 25 cases were classified as unifocal disease and 3 cases were multifocal single systemic diseases. In all cases, incisional biopsy was performed. After histologic confirmed, 14 cases was treated with curettage or surgical excision of the lesion and the other 14 cases were followed up without treatment. There is no death during follow up period. 11 cases has no radiological improvement after 3-6 months observation, intralesional steroid injection was performed. Conclusion: Patients with LCH who has rapid systemic onset is very rare, so if you meet the young children who suspected LCH, you shoulder avoid the examination which cause excessive radiation exposure to the young patient. In order to confirm the diagnosis of disease, biopsy is needed. Close observation after confirmed by histological method will bring the satisfactory results. But the patients who had pathologic fracture or wide bone destruction already may need curettage and bone grafting to lesion or internal fixation. The lesion which has no radiological improvement after 3-6 months observation or appear with pain interferes daily life may need local steroid injection as a good treatment.

Radiologic Evaluation of Limb Salvage Operation with Tumor Prosthesis (종양 대치물을 이용한 사지 구제술의 방사선학적 평가)

  • Moon, Sang-Ho;Lee, Sang-Hoon;Kim, Han-Soo;Oh, Joo-Han;Ko, Byung-Won;Koo, Ki-Hyung;Lee, Jae-Hag;Hwang, Chung-Soo;Lee, Han-Koo
    • The Journal of the Korean bone and joint tumor society
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    • v.6 no.4
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    • pp.152-162
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    • 2000
  • Purpose : To verify radiological changes of limb salvage operation using tumor prosthesis. Materials and Methods : Sixty-nine cases which used tumor prosthesis were reviewed. They have been followed up for average four years and nine months. We evaluated radiographs by ISOLS(International Symposium On Limb Salvage) radiological implants evaluation system immediate postoperatively, at postoperative 1 year and last follow-up. After converting 'excellent, good, fair, poor' to '4, 3, 2, 1' for stastical analysis, data were analyzed according to the use of cement, anatomical sites, diagnosis implant designs and age (<20 year vs. ${\geq}$20 year) using t-test and ANOVA. Results : The outcomes of cemented type prostheses were superior in remodelling and interface but inferior in anchorage. The scores of proximal femur and distal tibia were worse in bone remodelling. Osteosarcoma group had lower scores in anchorage and implant articular problem. There were no significant differences according to four different implant designs and age. Conclusion : In the intermediate term follow-up radiological evaluation, cemented type prosthesis were better in the aspects of bony resorption and osteolysis, and cementless one in anchorage. Distal femur and proximal tibia have higher scores in bony resorption, and osteosarcoma was worse tumor entity in anchorage and articular problem, and chemotherapy may be the cause.

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Tumor Suppressive Effect of Zoledronic Acid on Human Osteosarcoma Cells in Vivo (인간 골육종 세포주에서 Zoledronic acid의 종양 억제에 대한 생체내 실험)

  • Kim, Jae-Do;Seo, Tae-Hyuck;Lee, Dong-Won;Kwon, Young-Ho;Jang, Jae-Ho;Lee, Young-Goo
    • The Journal of the Korean bone and joint tumor society
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    • v.11 no.1
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    • pp.46-53
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    • 2005
  • Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

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