Expression Profiling of Genes Involved in Collagen Turnover in Tendons from Cerebral Palsy Patients

Department of Human Morphology, Extracellular Matrix Laboratory, University of Milan School of Medicine, Milan, Italy.
Connective tissue research (Impact Factor: 1.61). 02/2009; 50(3):203-8. DOI: 10.1080/03008200802613630
Source: PubMed


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 skeletal 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-beta1 (TGF-beta1), 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-beta1, and SPARC, suggesting that their tendons undergo higher mechanical loading stimulation.

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    • "Recently, altered gene expression in tendons of spastic muscle (Gagliano et al., 2009) as well as transcriptional upregulations have been hypothesized to alter, amongst other factors, extracellular matrix components (Smith et al., 2009). However, these transcriptional differences were found in both flexor and extensor muscles within the spastic arm. "
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