TY - JOUR
T1 - Expression profiling of genes involved in collagen turnover in tendons from cerebral palsy patients
AU - Gagliano, Nicoletta
AU - Pelillo, Francesco
AU - Chiriva-Internati, Maurizio
AU - Picciolini, Odoardo
AU - Costa, Francesco
AU - Schutt, Robert C.
AU - Gioia, Magda
AU - Portinaro, Nicola
N1 - Funding Information:
We thank the Ariel Foundation for the financial support to conduct this research study.
PY - 2009
Y1 - 2009
N2 - Cerebral palsy (CP) is a nonprogressive central nervous system lesion clinically characterized by impairment of voluntary movement related to spasticity, time of activation, and strength of scheletal muscle. Altered muscular control may act on tendon structure and influence extracellular matrix homeostasis, in particular, collagen. The effect of spasticity on collagen turnover in CP patients' tendons has not been described previously. We studied collagen turnover related genes in the gracilis and semitendinosus tendons of diplegic (n = 6) and quadriplegic (n = 15) patients, compared to normal subjects (n = 7). In particular, using real time RT-PCR, we analyzed the mRNA levels of the major extracellular matrix (ECM) components collagen type I (COL-I, alpha 2 chain COL1A2), the matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of MMP (TIMP-1), the enzyme responsible for collagen maturation lysyl hydroxylase 2b (LH2b), of the matricellular protein involved ECM remodelling (secreted protein acidic and rich in cysteine, SPARC), and the transforming growth factor-β1 (TGF-β1), a multipotent cytokine involved in collagen turnover. Our results show that gene expression profiles are quite different in CP samples compared to normal ones. In fact, spasticity induces relevant modifications of tendons at the molecular level, which modify their phenotypes to respond to the higher mechanical loading and increased functional demands. Interestingly, hypertonic quadriplegic subjects displayed the highest mRNA levels of COL1A2, LH2b, TGF-β1, and SPARC, suggesting that their tendons undergo higher mechanical loading stimulation.
AB - Cerebral palsy (CP) is a nonprogressive central nervous system lesion clinically characterized by impairment of voluntary movement related to spasticity, time of activation, and strength of scheletal muscle. Altered muscular control may act on tendon structure and influence extracellular matrix homeostasis, in particular, collagen. The effect of spasticity on collagen turnover in CP patients' tendons has not been described previously. We studied collagen turnover related genes in the gracilis and semitendinosus tendons of diplegic (n = 6) and quadriplegic (n = 15) patients, compared to normal subjects (n = 7). In particular, using real time RT-PCR, we analyzed the mRNA levels of the major extracellular matrix (ECM) components collagen type I (COL-I, alpha 2 chain COL1A2), the matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of MMP (TIMP-1), the enzyme responsible for collagen maturation lysyl hydroxylase 2b (LH2b), of the matricellular protein involved ECM remodelling (secreted protein acidic and rich in cysteine, SPARC), and the transforming growth factor-β1 (TGF-β1), a multipotent cytokine involved in collagen turnover. Our results show that gene expression profiles are quite different in CP samples compared to normal ones. In fact, spasticity induces relevant modifications of tendons at the molecular level, which modify their phenotypes to respond to the higher mechanical loading and increased functional demands. Interestingly, hypertonic quadriplegic subjects displayed the highest mRNA levels of COL1A2, LH2b, TGF-β1, and SPARC, suggesting that their tendons undergo higher mechanical loading stimulation.
KW - Cerebral Palsy
KW - Collagen Turnover
KW - Matrix Metalloproteinases
KW - SPARC
KW - Spasticity
KW - Tendons
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U2 - 10.1080/03008200802613630
DO - 10.1080/03008200802613630
M3 - Article
C2 - 19444761
AN - SCOPUS:67650488989
SN - 0300-8207
VL - 50
SP - 203
EP - 208
JO - Connective Tissue Research
JF - Connective Tissue Research
IS - 3
ER -