본문 바로가기
KERD
논문KCI 등재

Effects of CoCl2 on Osteogenic Differentiation of Human Mesenchymal Stem Cells

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

주제분류치의학

초록

Objective. To investigate the effects of the hypoxia inducible factor-1 (HIF-1) activation–mimicking agent cobalt chloride (CoCl2) on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and elucidate the underlying molecular mechanisms. Study design. The dose and exposure periods for CoCl2 in hMSCs were optimized by cell viability assays. After confirmation of CoCl2-induced HIF-1α and vascular endothelial growth factor expression in these cells by RT-PCR, the effects of temporary preconditioning with CoCl2on hMSC osteogenic differentiation were evaluated by RTPCR analysis of osteogenic gene expression, an alkaline phosphatase (ALP) activity assay and by alizarin red S staining. Results. Variable CoCl2 dosages (up to 500 μM) and exposure times (up to 7 days) on hMSC had little effect on hMSC survival. After CoCl2 treatment of hMSCs at 100 μM for 24 or 48hours, followed by culture in osteogenic differentiating media, several osteogenic markers such as Runx-2, osteocalcin and osteopontin, bone sialoprotein mRNA expression level were found to be up-regulated. Moreover, ALP activity was increased in these treated cells in which an accelerated osteogenic capacity was also verified by alizarin red S staining. Conclusions. The osteogenic differentiation potential of hMSCs could be preserved and even enhanced by CoCl2 treatment.

Abstract

Objective. To investigate the effects of the hypoxia inducible factor-1 (HIF-1) activation–mimicking agent cobalt chloride (CoCl2) on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and elucidate the underlying molecular mechanisms. Study design. The dose and exposure periods for CoCl2 in hMSCs were optimized by cell viability assays. After confirmation of CoCl2-induced HIF-1α and vascular endothelial growth factor expression in these cells by RT-PCR, the effects of temporary preconditioning with CoCl2on hMSC osteogenic differentiation were evaluated by RTPCR analysis of osteogenic gene expression, an alkaline phosphatase (ALP) activity assay and by alizarin red S staining. Results. Variable CoCl2 dosages (up to 500 μM) and exposure times (up to 7 days) on hMSC had little effect on hMSC survival. After CoCl2 treatment of hMSCs at 100 μM for 24 or 48hours, followed by culture in osteogenic differentiating media, several osteogenic markers such as Runx-2, osteocalcin and osteopontin, bone sialoprotein mRNA expression level were found to be up-regulated. Moreover, ALP activity was increased in these treated cells in which an accelerated osteogenic capacity was also verified by alizarin red S staining. Conclusions. The osteogenic differentiation potential of hMSCs could be preserved and even enhanced by CoCl2 treatment.

참고문헌 (56)

  1. Van der Kooy D, "Why stem cells?", Science, 287(5457), pp.1439~1441 (2000)
  2. Blau HM, "The evolving concept of a stem cell: entity or function?", Cell, 105(7), pp.829~841 (2001)
  3. Kopen GC, "Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains", Proc Natl Acad Sci, 96(19), pp.10711~10716 (1999)
  4. Pittenger MF, "Multilineage potential of adult human mesenchymal stem cells", Science, 284(5411), pp.143~147 (1999)
  5. Liechty KW, "Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep", Nat Med, 6(11), pp.1282~1286 (2000)
  6. Sanchez-Ramos J, "Adult bone marrow stromal cells differentiate into neural cells in vitro", Exp Neurol, 164(2), pp.247~256 (2000)
  7. Krause DS, "Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell", Cell, 105(3), pp.369~377 (2001)
  8. Soonyi Oh, "Induction of a Neuronal Phenotype from Human Bone Marrow-Derived Mesenchymal Stem Cells", International Journal of Oral Biology, 34(4), pp.177~183 (2009), 대한구강생물학회
  9. Eu Gene Park, "Establishment of High Throughput Screening System Using Human Umbilical Cord-derived Mesenchymal Stem Cells", International Journal of Oral Biology, 37(2), pp.43~49 (2012), 대한구강생물학회
  10. Cakouros, D, "Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A", Arf locus in mesenchymal stem cells, 2012, pp.32, 1433~1441
  11. Prockop DJ, "Marrow stromal cells as stem cells for nonhematopoietic tissues", Science, 276(5309), pp.71~74 (1997)
  12. Javazon EH, "Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells", Stem Cells, 19(3), pp.219~225 (2001)
  13. Cipolleschi MG, "The role of hypoxia in the maintenance of hematopoietic stem cells", Blood, 82(7), pp.2031~2037 (1993)
  14. Lennon DP, "Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: effects on in vitro and in vivo osteochondrogenesis", J Cell Physiol, 187(3), pp.345~355 (2001)
  15. Csete M, "Oxygen in the cultivation of stem cells", Ann N Y Acad Sci, 1049, pp.1~8 (2005)
  16. Ma T, "Hypoxia and stem cell-based engineering of mesenchymal tissues", Biotechnol Prog, 25(1), pp.32~42 (2009)
  17. Calvi, L. M., "Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells", Blood, 119, pp.2489~2499 (2012)
  18. Polykandriotis E, "Prevascularisation strategies in tissue engineering", Handchir Mikrochir Plast Chir, 38(4), pp.217~223 (2006)
  19. Malda J, "The roles of hypoxia in the in vitro engineering of tissues", Tissue Eng, 13(9), pp.2153~2162 (2007)
  20. Volkmer E, "Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone", Tissue Eng Part A, 14(8), pp.1331~1340 (2008)
  21. Grayson WL, "Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs", J Cell Physiol, 207(2), pp.331~339 (2006)
  22. Potier E, "Prolonged hypoxia concomitant with serum deprivation induces massive human mesenchymal stem cell death", Tissue Eng, 13(6), pp.1325~1331 (2007)
  23. Mylotte LA, "Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment", Stem Cells, 26(5), pp.1325~1336 (2008)
  24. Tuncay OC, "Oxygen tension regulates osteoblast function", Am J Orthod Dentofacial Orthop, 105(5), pp.457~463 (1994)
  25. Steinbrech DS, "Hypoxia regulates VEGF expression and cellular proliferation by osteoblasts in vitro", Plast Reconstr Surg, 104(3), pp.738~747 (1999)
  26. Warren SM, "Hypoxia regulates osteoblast gene expression", J Surg Res, 99(1), pp.147~155 (2001)
  27. Park JH, "Hypoxia decreases Runx2", Cbfa1 expression in human osteoblastlike cells, 2002, pp.192(1-2), 197~203
  28. Salim A, "Transient changes in oxygen tension inhibit osteogenic differentiation and Runx2 expression in osteoblasts", J Biol Chem, 279(38), pp.40007~40016 (2004)
  29. Pacary E, "Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells", J Cell Sci, 119(Pt 13), pp.2667~2678 (2006)
  30. Potier E, "Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression", Bone, 40(4), pp.1078~1087 (2007)
  31. Volkmer E, "Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation", Tissue Eng Part A, 16(1), pp.153~164 (2010)
  32. Jiang BH, "Transactivation and inhibitory domains of hypoxia-inducible factor 1 alpha. Modulation of transcriptional activity by oxygen tension", J Biol Chem, 272(31), pp.19253~19260 (1997)
  33. Chandel NS, "Mitochondrial reactive oxygen species trigger hypoxia-induced transcription", Proc Natl Acad Sci, 95(20), pp.11715~11720 (1998)
  34. Jung JY, "Inhibition by epigallocatechin gallate of CoCl2-induced apoptosis in rat PC12 cells", Life Sci, 80(15), pp.1355~1363 (2007)
  35. Isenmann, S., "TWIST family of basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stromal", Stem Cell Growth and Commitment, 2009, pp.27(10), 2457~2468
  36. Gunn, E.J., "The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma", Leukemia & lymphoma, 52, pp.1085~1097 (2011)
  37. Samineni, S., "Role of CEACAM1, ECM, and mesenchymal stem cells in an orthotopic model of human breast cancer", International journal of breast cancer, 381080 (2011)
  38. Mackenzie TC, "Human mesenchymal stem cells persist, demonstrate site-specific multipotential differentiation, and are present in sites of wound healing and tissue regeneration after transplantation into fetal sheep", Blood Cells Mol Dis, 27(3), pp.601~604 (2001)
  39. Reyes GD, "Map of candidate genes and STSs on 18p11.2, a bipolar disorder and schizophrenia susceptibility region", Mol Psychiatry, 7(4), pp.337~339 (2002)
  40. Wiedswang G, "Detection of isolated tumor cells in BM from breast-cancer patients: significance of anterior and posterior iliac crest aspirations and the number of mononuclear cells analyzed", Cytotherapy, 5(1), pp.40~45 (2003)
  41. Huang G, "Stabilization of cellular properties and differentiation mutilpotential of human mesenchymal stem cells transduced with hTERT gene in a long-term culture", J Cell Biochem, 103(4), pp.1256~1269 (2008)
  42. Pouysségur J, "Hypoxia signalling in cancer and approaches to enforce tumour regression", Nature, 441(7092), pp.437~443 (2006)
  43. Riddle RC, "Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling", J Mol Med, 87(6), pp.583~590 (2009)
  44. Wang Y, "The hypoxiainducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development", J Clin Invest, 117(6), pp.1616~1626 (2007)
  45. Maxwell PH, "Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth", Proc Natl Acad Sci, 94(15), pp.8104~8109 (1997)
  46. Dachs GU, "Targeting gene expression to hypoxic tumor cells", Nat Med, 3(5), pp.515~520 (1997)
  47. Datta SR, "Cellular survival: a play in three Akts", Genes Dev, 13(22), pp.2905~2927 (1999)
  48. Rosová I, "Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells", Stem Cells, 26(8), pp.2173~2182 (2008)
  49. Gnecchi M, "Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement", FASEB J, 20(6), pp.661~669 (2006)
  50. Liu X, "Lysophosphatidic acid protects mesenchymal stem cells against ischemia induced apoptosis in vivo", Stem cells Dev, 18(7), pp.947~954 (2009)
  51. Zhu W, "Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells", Stem Cells, 24(2), pp.416~425 (2006)
  52. Li W, "Bcl-2 engineered MSCs inhibited apoptosis and improved heart function", Stem Cells, 25(8), pp.2118~2127 (2007)
  53. Lord-Dufour S, "Evidence for transcriptional regulation of the glucose-6-phosphate transporter by HIF-1alpha: Targeting G6PT with mumbaistatin analogs in hypoxic mesenchymal stromal cells", Stem Cells, 27(3), pp.489~497 (2009)
  54. Wan C, "Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration", Proc Natl Acad Sci, 105(2), pp.686~691 (2008)
  55. Yang ZH, "Apical tooth germ cellconditioned medium enhances the differentiation of periodontal ligament stem cells into cementum", periodontal ligament- like tissues, 2009, pp.44(2), 199~210
  56. Ren H, "Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions", Biochem Biophys Res Commun, 347(1), pp.12~21 (2006)

관련 논문AI추천

Barium Stimulates the Expression of Osteogenic Genes in Human Mesenchymal Stem Cells into Osteoblasts in vitro김탁, 김선행, 안기훈, 이경욱, Hyun Tae Park, Jung Ho Shin, Jun Young Hur, So Eun Jung, Young Tae Kim대한폐경학회 · 대한폐경학회지2011 · 제17권 제2호Exploring upregulated genes during osteogenic differentiation of hMSCs권종진, 안세경, 이의석, 임재석, 장현석대한구강악안면외과학회 · 대한구강악안면외과학회지2008 · 제34권 제1호Bone Morphogenetic Protein Receptor in the Osteogenic Differentiation of Rat Bone Marrow Stromal CellsAnxun Wang, Shihu Sheng, Xueqiang Ding, Zhaoyou Yao연세대학교의과대학 · Yonsei Medical Journal2010 · 제51권 제5호Osteogenic potential of adult stem cells from human maxillary sinus membrane by Simvastatin in vitro: preliminary report김동준, 박재억, 윤경인대한구강악안면외과학회 · 대한구강악안면외과학회지2013 · 제39권 제4호Effects of immunosuppressants, FK506 and cyclosporin A, on the osteogenic differentiation of rat mesenchymal stem cells구영, 구기태, 김경화, 김수환, 김영성, 김태일, 류인철, 변유경, 설양조, 이용무대한치주과학회 · Journal of Periodontal & Implant Science2012 · 제42권 제3호Growth and Osteoblastic Differentiation of Mesenchymal Stem Cells on Silk Scaffolds강동철, 곽윤해, 권해용, 박영환, 백영애, 이광길, 전수연, 조유영, 조희연한국잠사학회 · International Journal of Industrial Entomology and Biomaterials2013 · 제27권 제2호

이 간행물의 다른 논문 (5건)