title: Alterations of overused supraspinatus tendon: a possible role of glycosaminoglycans and HARP/pleiotrophin in early tendon pathology.
abstract: Supraspinatus tendon overuse injuries lead to significant pain and disability in athletes and workers. Despite the prevalence and high social cost of these injuries, the early pathological events are not well known. We analyzed the potential relation between glycosaminoglycan (GAG) composition and phenotypic cellular alteration using a rat model of rotator cuff overuse. Total sulfated GAGs increased after 4 weeks of overuse and remained elevated up to 16 weeks. GAG accumulation was preceded by up-regulation of decorin, versican, and aggrecan proteoglycans (PGs) mRNAs and proteins and biglycan PG mRNA after 2 weeks. At 2 weeks, collagen 1 transcript decreased whereas mRNAs for collagen 2, collagen 3, collagen 6, and the transcription factor Sox9 were increased. Protein levels of heparin affine regulatory peptide (HARP)/pleiotrophin, a cytokine known to regulate developmental chondrocyte formation, were enhanced especially at 4 weeks, without up-regulation of HARP/pleiotrophin mRNA. Further results suggest that the increased GAGs present in early lesions may sequester HARP/pleiotrophin, which could contribute to a loss of tenocyte's phenotype. All these modifications are characteristic of a shift towards the chondrocyte phenotype. Identification of these early changes in the extra-cellular matrix may help to prevent the progression of the pathology to more disabling, degenerative alterations.
authors.affiliation: Laboratoire CRRET CNRS EAC 7149, Université Paris-Est Créteil, Cedex, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Attia
authors.forename: Alexander
authors.initials: A
authors.lastname: Scott
authors.forename: Arlette
authors.initials: A
authors.lastname: Duchesnay
authors.forename: Gilles
authors.initials: G
authors.lastname: Carpentier
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
authors.forename: Minh Bao
authors.initials: MB
authors.lastname: Huynh
authors.forename: Toin H
authors.initials: TH
authors.lastname: Van Kuppevelt
authors.forename: Camille
authors.initials: C
authors.lastname: Gossard
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Tassoni
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martelly
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D012090:Cumulative Trauma Disorders / Q000473:pathology* / Q000503:physiopathology*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006025:Glycosaminoglycans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000473:pathology / Q000502:physiology; D000070636:Rotator Cuff Injuries
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; C066845:pleiotrophin; C013786:A73025