title: Expression profiling of genes involved in collagen turnover in tendons from cerebral palsy patients.
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 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.
authors.affiliation: Department of Human Morphology, Extracellular Matrix Laboratory, University of Milan School of Medicine, Milan, Italy. nicoletta.gagliano@unimi.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Gagliano
authors.forename: Francesco
authors.initials: F
authors.lastname: Pelillo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
authors.forename: Odoardo
authors.initials: O
authors.lastname: Picciolini
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schutt
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.forename: Nicola
authors.initials: N
authors.lastname: Portinaro
mesh_terms: D000293:Adolescent; D002547:Cerebral Palsy / Q000235:genetics*; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D005109:Extracellular Matrix / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D015676:Osteonectin / Q000235:genetics; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013710:Tendons / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D024042:Collagen Type I; D015676:Osteonectin; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D003094:Collagen; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D020781:Matrix Metalloproteinase 1