Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

Abstract

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. Periostinwas found to differentially regulate the apoptosis, proliferation, α 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.

The association between Peyronie's and Dupuytren's disease

“…[8][9][10] DD is a fibroproliferative condition of the palmar fascias in the hand, typically resulting in progressive contracture of one or more fingers. 11 DD is thought to be the most common hereditary connective tissue disorder in Caucasians. 12 The prevalence of DD in different geographical locations is extremely variable (0.2-56%), and its not clear whether this is genetic, environmental or a combination of both.…”

Functional significance of periostin in excisional skin repair

“…In fact, rhPN has been shown to increase both proliferation and myofibroblastic behavior in palmar fascia fibroblasts. 18 Upon closer inspection, however, it is clear that the evidence presented in the three reports on skin repair could arise as a result of differences in experimental methodologies.…”

“…DD cells in 3D culture induced a-SMA in response to rhPN. 18 Vi 2009: Growth on rhPN coated plates resulted in an increase in proliferation of palmar fascia fibroblasts. 18 Sidhu 2010: Transfection of bronchial epithelial cells (BEAS2B) with a rhPN expression vector resulted in increased a-SMA protein and mRNA.…”

“…18 Vi 2009: Growth on rhPN coated plates resulted in an increase in proliferation of palmar fascia fibroblasts. 18 Sidhu 2010: Transfection of bronchial epithelial cells (BEAS2B) with a rhPN expression vector resulted in increased a-SMA protein and mRNA. 23 Liu 2011: Periostin-silenced gastric cancer cells exhibited reduced cell proliferation.…”

Molecular mechanisms and treatment strategies for Dupuytren’s disease

“…This type of study using differential gene expression analysis, combined with molecular and functional studies of disease tissues and cells, has helped identify a number of putative abnormal mediators in DD. Several dysregulated genes in DD encode secreted ECM proteins, [60][61][62][63][64] and these may play a role in disease progression or recurrence. While structural components of the ECM, such as collagens, laminin, fibronectin, and elastin are altered in DD, 65,66 recent work has also identified proteases, including A Disintegrin and Metalloprotease (ADAM)-12, proteoglycans (notably PRG4), and "matricellular" components, including tenascin C and periostin, as well as specific members of the MMP family (MMP-2 and MMP-9) mentioned earlier, as being abnormally regulated.…”