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HDAC4在核内外穿梭和降解控制骨骺的生长和发育机制研究
  • 项目名称：HDAC4在核内外穿梭和降解控制骨骺的生长和发育机制研究
  • 项目类别：面上项目
  • 批准号：81171676
  • 申请代码：H0601
  • 项目来源：国家自然科学基金
  • 研究期限：2012-01-01-2015-12-31
  • 项目负责人：魏垒
  • 依托单位：山西医科大学
  • 批准年度：2011
中文摘要：

骨骺决定长骨的长度和形状，但调控机制仍不清楚。长骨的延长是通过内源性成骨来完成的。这个过程包括骨骺软骨细胞分裂，分化，肥大，程序死亡，吸收及骨的吸收。我们最近研究发现HDAC4在核内外穿梭和降解控制骨骺的生长和发育。过程通过HDAC4和Runx2的结合并抑制其活性来完成。Runx2是一个极其重要的转录因子，控制着软骨细胞和骨细胞的分化。本研究采用体内和体外的模型去探索1.Ca2+ / Calmodulin 信号通路控制HDAC4核内-核外 的穿梭，从而达到调控软骨细胞从分裂进入成熟状态。2. p38 MAPK通过控制Caspases 去调控HDAC4的降解，从而达到调控软骨细胞从成熟进入肥大状态。了解骨骺的分子生物调控机制，将使我们有可能预防和治疗与骨骺生长有关的疾病，如肢体的不等长，侏儒和骨软骨病；理解骨骺软骨细胞分裂，分化，成熟的分子生物学机制也有助于我们了解骨关节病。

中文主题词： 骨骺；HDAC4；生长和发育；；
英文摘要：

Epiphysis；HDAC4；growth and development；；

英文主题词： Epiphysis；HDAC4；growth and development；；
结论摘要：

骨骺决定长骨的长度和形状，但调控机制仍不清楚。长骨的延长是通过内源性成骨来完成的。这个过程包括骨骺软骨细胞分裂，分化，肥大，程序死亡，吸收及骨的吸收。我们前期研究发现HDAC4细胞核内外穿梭和降解调节骨骺的生长和发育。该过程通过HDAC4和Runx2的结合并抑制其活性来完成。Runx2是一个极其重要的转录因子，控制着软骨细胞和骨细胞的分化。本研究采用体内和体外实验对其机制进行探索，发现CaMKIV信号通路调控HDAC4核内-核外穿梭，进而调控软骨细胞肥大；p38 MAPK通过调节Caspases活性达到调控HDAC4降解，进而调节软骨细胞进入肥大状态。了解骨骺的分子生物调控机制，将使我们有可能预防和治疗与骨骺生长有关的疾病，如肢体的不等长，侏儒和骨软骨病；理解骨骺软骨细胞分裂，分化，成熟的分子生物学机制也有助于我们了解骨关节病。

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期刊论文
Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway.
Decreased histone deacetylase 4 is associated with human osteoarthritis cartilage degeneration by re
Attenuation of cartilage pathogenesis in post-traumatic osteoarthritis (PTOA) in mice by blocking th
MicroRNA-1 Regulates Chondrocyte Phenotype by Repressing Histone Deacetylase 4 during Growth Plate D
Indian hedgehog contributes to human cartilage endplate degeneration
Identification of alpha1-Antitrypsin as a Potential Candidate for Internal Control for Human Synovia
Expansion on matrix deposited by nonchondrogenic urine stem cells strengthens repeated passage bone
Identification of Alpha 2 Macroglobulin (A2M) as a master inhibitor of cartilage degrading factors t
Indian hedgehog in synovial fluid is a novel marker for early cartilage lesions in human knee joint
Indian Hedgehog, a Critical Modulator in Osteoarthritis, could be a Potential Therapeutic Target for
Nutrition and degeneration of articular cartilage.
Type II collagen fragment HELIX-II is a marker for early cartilage lesions but does not predict prog
The age-related changes in cartilage and osteoarthritis.
Demineralized Bone Matrix Combined Bone Marrow Mesenchymal Stem Cells, Bone Morphogenetic Protein-2
Subcellular Relocation of Histone Deacetylase 4 Regulates Growth Plate Chondrocyte Differentiation t
Specific inhibition of HDAC4 in cardiac progenitor cells enhances myocardial repairs.
Mitogen-activated Protein Kinase p38 Induces HDAC4 Degradation in Hypertrophic Chondrocytes
Effect of the disruption of three cytoskeleton components on chondrocyte metabolism in rabbit knee c
MicroRNA Regulates Vascular Endothelial Growth Factor Expression in Chondrosarcoma Cells.
Mitogen-activated protein kinase p38 induces HDAC4 degradation in hypertrophic chondrocytes.
Anti-Catabolic Effect of Caffeic Acid Phenethyl Ester, an Active Component of Honeybee Propolis on B
miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis
组蛋白去乙酰化酶4在软骨与骨发育中的调控机制
人血液中YKL-40浓度变化与膝关节退变关系的Meta分析
会议论文
India Hedgehog is correlated to Human Endplate Cartilage Degeneration.
P38 Mitogen-activated Protein Kinase Regulates HDAC4 Degradation In Growth Plate Chondrocytes.
Decreased Hdac4 Plays A Critical Role In Human Oa Cartilage Degeneration By Releasing Hdac4 Inhibiti
Abnormal Mechanical Loading Induces Cartilage Degeneration By Accelerating Meniscus Hypertrophy And
Blocking Hypoxia-Induced Production of CXCR4 by AMD3100 Inhibits Cartilage Degradation.
Identification Of Alpha 2 Macroglobulin (a2m) As A Master Inhibitor To Attenuate Post-traumatic Oste
Decrease of HDAC4 is associated with OA cartilage degeneration by up-regulating OA related genes.
The Role of Indian Hedgehog (Ihh) in Fibular Fracture Healing in Col2a1-CreER; Ihhfl/fl and WT Mice.
Blocking CXCR4 attenuates PTOA pathogenesis.
Blocking of the SDF-1/CXCR4 Pathway Inhibits OA Cartilage Degeneration.
Indian Hedgehog is not required for Fibular Fracture Healing in Col2a1-CreER; Ihhfl/fl Mice.
A Decrease of the Cytoskeleton Components is associated with an alteration of Viscoelastic Propertie
A-2-Macroglobulin Inhibits Inflammatory Cytokines and MMPs in Osteoarthritis.
Blockage of SDF-1/CXCR4 by AMD3100 attenuates guinea pig OA cartilage degeneration.
Deletion of Indian Hedgehog attenuates OA progression in human OA cartilage and Col2a1-CreERT2; Ihhf
Disrupting Ihh signaling pathway in vivo attenuates OA progression in Col2a1-CreERT2; Ihhfl/fl mouse
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