Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells.
Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.
Vi
Linda
L
Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, London, Ontario, Canada.
Feng
Lucy
L
Zhu
Rebecca D
RD
Wu
Yan
Y
Satish
Latha
L
Gan
Bing Siang
BS
O'Gorman
David B
DB
D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001696:Biomechanical Phenomena / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004387:Dupuytren Contracture / Q000378:metabolism / Q000473:pathology*; D005205:Fascia / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008663:Metacarpus / Q000378:metabolism / Q000473:pathology*; D013314:Stress, Mechanical
C541116:ACTA2 protein, human; D000199:Actins; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human