title: Expression analysis of genes involved in collagen cross-linking and its regulation in traumatic anterior shoulder instability.
abstract: The molecular alterations involved in the capsule deformation presented in shoulder instability patients are poorly understood. Increased TGFβ1 acts as a signal for production of matrix macromolecules by fibrogenic cells at joint injury sites. TGFβ1, through its receptor TGFβR1, regulates genes involved in collagen cross-linking, such as LOX, PLOD1, and PLOD2. We evaluated TGFβ1, TGFβR1, LOX, PLOD1, and PLOD2 gene expression in the antero-inferior (macroscopically injured region), antero-superior and posterior regions of the glenohumeral capsule of 29 shoulder instability patients and eight controls. We observed that PLOD2 expression was increased in the anterior-inferior capsule region of the patients compared to controls. LOX expression tended to be increased in the posterior portion of patients. Patients with recurrent shoulder dislocation presented upregulation of TGFβR1 in the antero-inferior capsule portion and of PLOD2 in the posterior region. Conversely, LOX was increased in the posterior portion of the capsule of patients with a single shoulder dislocation episode. In the antero-inferior, LOX expression was inversely correlated and TGFβR1 was directly correlated with the duration of symptoms. In the posterior region, PLOD2, TGFβ1, and TGFβR1 were directly correlated with the duration of symptoms. In conclusion, PLOD2 expression was increased in the macroscopically injured region of the capsule of patients. Upregulation of TGFβ1, TGFβR1, and PLOD2 seems to be related with the maintenance of disease symptoms, especially in the posterior region. LOX upregulation seems to occur only in the initial phase of the affection. Therefore, TGFβ1, TGFβR1, LOX, and PLOD2 may play a role in shoulder instability.
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Paulo Santoro
authors.initials: PS
authors.lastname: Belangero
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.|Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, São Paulo, 04023-001, Brazil.
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Carina
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, São Paulo, 04023-001, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Figueiredo
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, São Paulo, 04023-001, Brazil.
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Carlos Vicente
authors.initials: CV
authors.lastname: Andreoli
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Alberto
authors.initials: A
authors.lastname: de Castro Pochini
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Benno
authors.initials: B
authors.lastname: Ejnisman
authors.affiliation: Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, São Paulo, 04038-031, Brazil.
authors.forename: Moises
authors.initials: M
authors.lastname: Cohen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D012783:Shoulder Dislocation / Q000378:metabolism*; D012785:Shoulder Joint / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003094:Collagen
keywords: TGFβ1 signaling; collagen cross-linking; gene expression; shoulder instability