title: Enhanced tissue regeneration potential of juvenile articular cartilage.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To compare the biological properties and tissue regeneration capabilities of juvenile and adult bovine articular cartilage.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rhonda B. Clarke, MS, Zimmer Orthobiologics Inc, 9301 Amberglen Boulevard, Building J, Suite 100, Austin, TX 78729. rhonda.clarke@zimmer.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Zhao
authors.forename: Rhonda B
authors.initials: RB
authors.lastname: Clarke
authors.forename: Jizong
authors.initials: J
authors.lastname: Gao
authors.forename: Ian R
authors.initials: IR
authors.lastname: Garrett
authors.forename: Ed E C
authors.initials: EE
authors.lastname: Margerrison
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology*; D002417:Cattle; D002452:Cell Count; D049109:Cell Proliferation; D019902:Chondrocytes / Q000502:physiology*; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012038:Regeneration
chemical_list: D006025:Glycosaminoglycans; D020778:Matrix Metalloproteinase 2
keywords: adult; aging; articular cartilage; biology of cartilage; bovine; cartilage regeneration; cartilage repair; chondrocyte; gene expression; juvenile; knee; migration