Expression profiling of genes involved in collagen turnover in tendons from cerebral palsy patients

Nicoletta Gagliano, Francesco Pelillo, Maurizio Chiriva-Internati, Odoardo Picciolini, Francesco Costa, Robert C. Schutt, Magda Gioia, Nicola Portinaro

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalConnective Tissue Research
Volume50
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • Cerebral Palsy
  • Collagen Turnover
  • Matrix Metalloproteinases
  • SPARC
  • Spasticity
  • Tendons

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Orthopedics and Sports Medicine
  • Rheumatology

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