Liu Hui, Zhao Zhixing, Clarke Rhonda B, Gao Jizong, Garrett Ian R, Margerrison Ed E C
Rhonda B. Clarke, MS, Zimmer Orthobiologics Inc, 9301 Amberglen Boulevard, Building J, Suite 100, Austin, TX 78729.
Am J Sports Med. 2013 Nov;41(11):2658-67. doi: 10.1177/0363546513502945. Epub 2013 Sep 16.
Articular cartilage undergoes substantial age-related changes in molecular composition, matrix structure, and mechanical properties. These age-related differences between juvenile and adult cartilage manifest themselves as markedly distinct potentials for tissue repair and regeneration.
To compare the biological properties and tissue regeneration capabilities of juvenile and adult bovine articular cartilage.
Controlled laboratory study.
Articular cartilage harvested from juvenile (age, 4 months) and adult (age, 6-8 years) bovine femoral condyles was cultured for 4 weeks to monitor chondrocyte migration, glycosaminoglycan content conservation, and new tissue formation. The cartilage cell density and proliferative activity were also compared. Additionally, the effects of age-related changes on cartilage gene expression were analyzed using the Affymetrix GeneChip array.
Compared with adult cartilage, juvenile bovine cartilage demonstrated a significantly greater cell density, higher cell proliferation rate, increased cell outgrowth, elevated glycosaminoglycan content, and enhanced matrix metallopeptidase 2 activity. During 4 weeks in culture, only juvenile cartilage was able to generate new cartilaginous tissues, which exhibited pronounced labeling for proteoglycan and type II collagen but not type I collagen. With over 19,000 genes analyzed, distinctive gene expression profiles were identified. The genes mostly involved in cartilage growth and expansion, such as COL2A1, COL9A1, MMP2, MMP14, and TGFB3, were upregulated in juvenile cartilage, whereas the genes primarily responsible for structural integrity, such as COMP, FN1, TIMP2, TIMP3, and BMP2, were upregulated in adult cartilage.
As the first comprehensive comparison between juvenile and adult bovine articular cartilage at the tissue, cellular, and molecular levels, the results strongly suggest that juvenile cartilage possesses superior chondrogenic activity and enhanced regenerative potential over its adult counterpart. Additionally, the differential gene expression profiles of juvenile and adult cartilage suggest possible mechanisms underlying cartilage age-related changes in their regeneration capabilities, structural components, and biological properties.
The results of this comparative study between juvenile and adult bovine articular cartilage suggest an enhanced regenerative potential of juvenile cartilage tissue in the restoration of damaged articular cartilage.
关节软骨在分子组成、基质结构和力学性能方面会经历与年龄相关的显著变化。幼年和成年软骨之间这些与年龄相关的差异表现为组织修复和再生潜力明显不同。
比较幼年和成年牛关节软骨的生物学特性和组织再生能力。
对照实验室研究。
从幼年(4个月龄)和成年(6 - 8岁)牛股骨髁采集关节软骨,培养4周以监测软骨细胞迁移、糖胺聚糖含量维持和新组织形成。还比较了软骨细胞密度和增殖活性。此外,使用Affymetrix基因芯片阵列分析与年龄相关变化对软骨基因表达的影响。
与成年软骨相比,幼年牛软骨表现出显著更高的细胞密度、更高的细胞增殖率、增加的细胞迁出、升高的糖胺聚糖含量以及增强的基质金属蛋白酶2活性。在培养4周期间,只有幼年软骨能够产生新的软骨组织,其蛋白聚糖和II型胶原标记明显,但I型胶原无标记。分析了超过19000个基因后,鉴定出了独特的基因表达谱。在幼年软骨中,大多参与软骨生长和扩张的基因,如COL2A1、COL9A1、MMP2、MMP14和TGFB3上调,而在成年软骨中,主要负责结构完整性的基因,如COMP、FN1、TIMP2、TIMP3和BMP2上调。
作为首次在组织、细胞和分子水平对幼年和成年牛关节软骨进行的全面比较,结果强烈表明幼年软骨比成年软骨具有更强的软骨生成活性和更高的再生潜力。此外,幼年和成年软骨的差异基因表达谱提示了软骨在再生能力、结构成分和生物学特性方面与年龄相关变化的潜在机制。
幼年和成年牛关节软骨的这项比较研究结果表明,幼年软骨组织在修复受损关节软骨方面具有增强的再生潜力。