Differential gene expression associated with postnatal equine articular cartilage maturation.
BACKGROUND
Articular cartilage undergoes an important maturation process from neonate to adult that is reflected by alterations in matrix protein organization and increased heterogeneity of chondrocyte morphology. In the horse, these changes are influenced by exercise during the first five months of postnatal life. Transcriptional profiling was used to evaluate changes in articular chondrocyte gene expression during postnatal growth and development.


METHODS
Total RNA was isolated from the articular cartilage of neonatal (0-10 days) and adult (4-5 years) horses, subjected to one round of linear RNA amplification, and then applied to a 9,367-element equine-specific cDNA microarray. Comparisons were made with a dye-swap experimental design. Microarray results for selected genes (COL2A1, COMP, P4HA1, TGFB1, TGFBR3, TNC) were validated by quantitative polymerase chain reaction (qPCR).


RESULTS
Fifty-six probe sets, which represent 45 gene products, were up-regulated (p < 0.01) in chondrocytes of neonatal articular cartilage relative to chondrocytes of adult articular cartilage. Conversely, 586 probe sets, which represent 499 gene products, were up-regulated (p < 0.01) in chondrocytes of adult articular cartilage relative to chondrocytes of neonatal articular cartilage. Collagens, matrix-modifying enzymes, and provisional matrix non-collagenous proteins were expressed at higher levels in the articular cartilage of newborn foals. Those genes with increased mRNA abundance in adult chondrocytes included leucine-rich small proteoglycans, matrix assembly, and cartilage maintenance proteins.


CONCLUSIONS
Differential expression of genes encoding matrix proteins and matrix-modifying enzymes between neonates and adults reflect a cellular maturation process in articular chondrocytes. Up-regulated transcripts in neonatal cartilage are consistent with growth and expansion of the articular surface. Expression patterns in mature articular cartilage indicate a transition from growth to homeostasis, and tissue function related to withstanding shear and weight-bearing stresses.
Mienaltowski
Michael J
MJ
University of Kentucky, Department of Veterinary Science, M.H. Gluck Equine Research Center, Lexington, KY 40546-0099, USA. M.Mski@uky.edu
Huang
Liping
L
Stromberg
Arnold J
AJ
MacLeod
James N
JN
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000254:growth & development* / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006128:Growth / Q000235:genetics / Q000502:physiology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006736:Horses / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology
D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D019063:Tenascin; D053773:Transforming Growth Factor beta1; C071736:betaglycan