AGING HUMAN ARTICULAR CARTILAGE--BIOMECHANICS AND REPAIR
AGING HUMAN ARTICULAR CARTILAGE--BIOMECHANICS AND REPAIR
批准号:
6234154
负责人:
Robert L Sah
金额:
$20.66万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-07-01 至 1998-03-31
中文摘要
骨关节炎是影响腹泻的最常见的人类疾病。
关节,并在老化过程中变得越来越普遍。长期的
这个项目的目标是进一步从分子水平上理解
(1)人体关节软骨的生物力学功能
衰老和骨关节炎,以及(2)衰老和骨关节炎的功能修复
患病的人类关节软骨。随着年龄的增长,人类关节
软骨细胞密度下降,钙离子增加-
含有晶体,阴离子糖胺聚糖含量增加,
以及胶原网的变化(变性胶原蛋白增加
和戊二胺交联物)。这些组织成分的变化
可能是压力随年龄和深度变化的基础,
关节软骨的拉伸和断裂力学特性。
组成-功能关系将通过以下方式进行评估和测试
选择性地改变组织成分(例如,耗尽
糖胺多聚糖和诱导细胞凋亡)。软骨修复是
依赖于活跃的组织新陈代谢。从概念上讲,软骨修复
包括填充相当大的缺陷和整合
对位的组织区域。转化生长因子-β1是先前发现的
作为一种对人类软骨细胞增殖的有效刺激。转化生长因子-β1
也刺激软骨细胞产生核苷酸
焦磷水解酶(NTPPPH),产生焦磷酸盐和
可能影响细胞代谢和胞外晶体沉积。
人的软骨,NTPPPH活性主要是由于膜
糖蛋白,PC-1。与年龄相关的软骨细胞减少
增殖性和分泌性反应以及
对转化生长因子-β1的反应性和PC-1/NTPPPH的表达可能
影响老化细胞进行修复反应的能力。为了测试
这种可能性,转化生长因子-β1在年龄相关调节中的作用
软骨细胞或软骨膜细胞形成软骨组织
在体外长期培养的聚乳酸支架内将
此外,PC-1过度表达的影响将是
下定决心。此外,基质重塑机制参与了
完整的修复将使用软骨的体外模型进行评估
外植体。最后,常驻软骨细胞的年龄相关变化或
软骨的生物力学特性可能会改变其生物力学性能。
细胞生物合成的调控。为了测试这种可能性,
人全层关节软骨的生物合成反应
外植体对静态和动态负载的评估将与
深度变化的物理信号。流体流动对软骨细胞的影响
将被独立审查。
英文摘要
Osteoarthritis is the most common human disease affecting diarthrodial
joints, and becomes increasing prevalent during aging. The long-term
goal of this project is to further the molecular-level understanding of
(1) the biomechanical function of human articular cartilage during
aging and osteoarthritis, and (2) the functional repair of aging and
diseased human articular cartilage. With aging, human articular
cartilage undergoes a decrease in cell density, an increase in calcium-
containing crystals, an increase in anionic glycosaminoglycan content,
and changes in the collagen meshwork (increases in denatured collagen
and pentosidine cross-links). The variation in these tissue components
may underlie age- and depth-dependent variations in the compressive,
tensile, and fracture mechanical properties of articular cartilage.
Composition-function relationships will be assessed and then tested by
selectively altering the tissue composition (e.g., depletion of
glycosaminoglycan and induction of apoptosis). Cartilage repair is
dependent on active tissue metabolism. Conceptually, cartilage repair
involves both the filling of sizable defects and the integration of
regions of tissue in apposition. TGF-beta1 was previously identified
as a potent stimulus for human chondrocyte proliferation. TGF-beta1
also stimulated chondrocyte production of nucleotide
pyrophosphohydrolase (NTPPPH), which generates pyrophosphate and
may affect cell metabolism and extracellular crystal deposition.
Inhuman cartilage, NTPPPH activity is due primarily to the membrane
glycoprotein, PC-1. Age-related decreases in chondrocyte
proliferative and secretory responses as well as changes in
responsiveness to TGF-beta1 and elaboration of PC-1/NTPPPH may
affect the ability of aging cells to mount a repair response. To test
this possibility, the age-related role of TGF-beta1 in regulating
cartilaginous tissue formation by chondrocytes or perichondrial cells
within a polylactic acid scaffold during long-term culture in vitro will
be assessed; also, the effect of overexpression of PC-1 will be
determined. Further, the matrix remodeling mechanisms involved in
integrative repair will be assessed using an in vitro model of cartilage
explants. Finally, age-related changes in the resident chondrocytes or
cartilage biomechanical properties may alter the biomechanical
regulation of cell biosynthesis. To test this possibility, the
biosynthetic response of full thickness human articular cartilage
explants to static and dynamic loads will be assessed and related to the
depth-varying physical signals. Fluid flow effects on chondrocytes
will be examined independently.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Mechanisms of Articular Cartilage Lubrication
-
批准号:8074678
-
项目类别:
-
资助金额:$3.67万
-
财政年份:2010
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7903846
-
项目类别:
-
资助金额:$18.4万
-
财政年份:2009
-
负责人:Robert L Sah
-
依托单位:
COLLAGEN STRUCTURE UNDER TENSION W/ DEPTH AND AGE VARIATION IN BOVINE CARTILAGE
-
批准号:7722450
-
项目类别:
-
资助金额:$0.1万
-
财政年份:2008
-
负责人:Robert L Sah
-
依托单位:
TERMIS-NA 2008 Annual Conference & Exposition
-
批准号:7615174
-
项目类别:
-
资助金额:$3.3万
-
财政年份:2008
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7417751
-
项目类别:
-
资助金额:$32.34万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7232354
-
项目类别:
-
资助金额:$33.0万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7590096
-
项目类别:
-
资助金额:$15.45万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7596402
-
项目类别:
-
资助金额:$32.34万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7147152
-
项目类别:
-
资助金额:$33.98万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Mechanisms of Articular Cartilage Lubrication
-
批准号:7770800
-
项目类别:
-
资助金额:$32.02万
-
财政年份:2006
-
负责人:Robert L Sah
-
依托单位:
Cartilage Integration: in Vitro to In Vivo Translation
-
批准号:7049745
-
项目类别:
-
资助金额:$22.59万
-
财政年份:2005
-
负责人:Robert L Sah
-
依托单位:
Cartilage Integration: in Vitro to In Vivo Translation
-
批准号:7140680
-
项目类别:
-
资助金额:$17.25万
-
财政年份:2005
-
负责人:Robert L Sah
-
依托单位:
GRC on Musculoskeletal Biology & Bioengineering
-
批准号:6756723
-
项目类别:
-
资助金额:$2.4万
-
财政年份:2004
-
负责人:Robert L Sah
-
依托单位:
GRC on Musculoskeletal Biology and Bioengineering
-
批准号:6460478
-
项目类别:
-
资助金额:$2.1万
-
财政年份:2002
-
负责人:Robert L Sah
-
依托单位:
CORE--CELL AND TISSUE CULTURE
-
批准号:6600049
-
项目类别:
-
资助金额:$15.83万
-
财政年份:2002
-
负责人:Robert L Sah
-
依托单位:
CORE--CELL AND TISSUE CULTURE
-
批准号:6610356
-
项目类别:
-
资助金额:$15.83万
-
财政年份:2002
-
负责人:Robert L Sah
-
依托单位:
MECHANISMS & ENHANCEMENT OF INTEGRATIVE CARTILAGE REPAIR
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批准号:6699664
-
项目类别:
-
资助金额:$31.01万
-
财政年份:2000
-
负责人:Robert L Sah
-
依托单位:
MECHANISMS & ENHANCEMENT OF INTEGRATIVE CARTILAGE REPAIR
-
批准号:6628105
-
项目类别:
-
资助金额:$30.24万
-
财政年份:2000
-
负责人:Robert L Sah
-
依托单位:
MECHANISMS & ENHANCEMENT OF INTEGRATIVE CARTILAGE REPAIR
-
批准号:6497419
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项目类别:
-
资助金额:$29.44万
-
财政年份:2000
-
负责人:Robert L Sah
-
依托单位:
MECHANISMS & ENHANCEMENT OF INTEGRATIVE CARTILAGE REPAIR
-
批准号:6045897
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项目类别:
-
资助金额:$29.33万
-
财政年份:2000
-
负责人:Robert L Sah
-
依托单位:
海外基金