COLLAGEN IN OSTEOARTHRITIC CARTILAGE

骨关节炎软骨中的胶原蛋白

• 批准号: 3151006
• 负责人: Paul David Benya
• 金额: $ 14.24万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-03-15 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151006
• 关键词: articular cartilage; cartilage disorder; cell differentiation; cell growth regulation; chondrocytes; hormone regulation /control mechanism; human subject; mucopolysaccharides; organ culture; osteoarthritis; proteoglycan; synovial fluid

The proposed research is directed toward understanding 1) the factors which modulate the differentiated state of chondrocytes, and 2) the hormonal regulation or cartilage matrix synthesis. We have observed that dedifferentiated chondrocytes will return to the differentiated state if changed to spherical shape in agarose suspension culture. Cytoskeletal involvement in phenotypic switching is indicated because dedifferentiated monolayer chondrocytes will reexpress the differentiated collagen phenotype after treatment with the microfilament-disruptive drug, cytochalasin B. We will document and expand this information on a microfilament-dependent pathway for gene regulation in chondrocytes. We have hypothesized that the increased rate of proteoglycan (PG) and collagen synthesis (8-fold) that occurs during in vitro culture of articular cartilage slices is due to an increase in the number of somatomedin receptors per cell. Following an initial lack of serum dose response, original chondrocytes and their progeny in agarose, monolayer, and slice cultures become dose responsive as measured by PG and DNA synthesis. Radiolabeled growth factors will be used to probe for parallel increases in receptor number/cell. If we can understand the mechanism of this increase in cellular responsiveness to serum we may be able to increase matrix synthesis in osteoarthritis and greatly decrease the cartilage destruction that follows proteoglycan depletion. These studies will be performed with rabbit humeral articular cartilage and chondrocytes. Collagen phenotypes will be routinely determined by SDS electrophoresis and 2-D CNBr peptide maps of isolated collagens. Understanding the mechanism that stabilize the chondrocyte phenotype and enhance matrix synthesis may facilitate the design of therapeutic strategies that stimulate resistance to the initiation and progression of osteoarthritis.

提出的研究旨在了解1)因素

项目成果

Coordinate regulation of type IX and type II collagen synthesis during growth of chick chondrocytes in retinoic acid or 5-bromo-2'-deoxyuridine.

在视黄酸或 5-溴-2-脱氧尿苷中鸡软骨细胞生长过程中协调 IX 型和 II 型胶原合成的调节。

• 发表时间: 1986
• 期刊: The Journal of biological chemistry
• 作者: Yasui,N;Benya,PD;Nimni,ME
• 通讯作者: Nimni,ME