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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 19 - 25 (7page)
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Osteocytes may function as mechanotransducers byregulating local osteoclastogenesis. Reduced availability ofoxygen, i.e. hypoxia, could occur during disuse, bonedevelopment, and fracture. Receptor activator of nuclearfactor-κB ligand (RANKL) is an osteoblast/stromal cellderived essential factor for osteoclastogenesis. The hypoxiainduced osteoclastogenesis via increased RANKL expressionin osteoblasts was demonstrated. Hypoxic regulation of geneexpression generally involves activation of thehypoxia-inducible factor (HIF) transcription pathway. In thepresent study, we investigated whether hypoxia regulatesRANKL expression in murine osteocytes and HIF-1αmediates hypoxia-induced RANKL expression bytransactivating RANKL promoter, to elucidate the role ofosteocyte in osteoclastogenesis in the context of hypoxiccondition. The expression levels of RANKL mRNA andprotein, as well as hypoxia inducible factor-1α (HIF-1α)protein, were significantly increased in hypoxic condition inMLO-Y4s. Constitutively active HIF-1α alone significantlyincreased the levels of RANKL expression in MLO-Y4sunder normoxic conditions, whereas dominant negativeHIF-1α blocked hypoxia-induced RANKL expression. Tofurther explore to find if HIF-1α directly regulates RANKLtranscription, a luciferase reporter assay was conducted.
Hypoxia significantly increased RANKL promoter activity,whereas mutations of putative HIF-1α binding elements inRANKL promoter prevented this hypoxia-induced RANKLpromoter activity in MLO-Y4s. These results suggest thatHIF-1α mediates hypoxia-induced up-regulation of RANKLexpression, and that in osteocytes of mechanically unloadedbone, hypoxia enhances osteoclastogenesis, at least in part, viaan increased RANKL expression in osteocytes.
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참고문헌 (23)
참고문헌 신청
Agnieszka Loboda / 2010 / HIF-1 and HIF-2 Transcription Factors - Similar but Not Identical / Molecules and Cells 29 (5) : 435 ~ 442
Amarilio R / 2007 / HIF1α regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis / Development 134 : 3917
Arnett TR / 2003 / Hypoxia is a major stimulator of osteoclast formation and bone resorption / J Cell Physiol 196 : 2 ~ 8
Brighton CT / 1972 / Oxygen tension of healing fractures in the rabbit / J Bone Joint Surg Am 54 : 323 ~ 332
Chun YS / 2002 / A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1α gene / Biochem J 362 : 71 ~ 79
Amarilio R / 2007 / HIF1α regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis / Development 134 : 3917
Arnett TR / 2003 / Hypoxia is a major stimulator of osteoclast formation and bone resorption / J Cell Physiol 196 : 2 ~ 8
Brighton CT / 1972 / Oxygen tension of healing fractures in the rabbit / J Bone Joint Surg Am 54 : 323 ~ 332
Chun YS / 2002 / A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1α gene / Biochem J 362 : 71 ~ 79
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