Functional role of periostin in development and wound repair: implications for connective tissue disease

Abstract

Integrity of the extracellular matrix (ECM) is essential for maintaining the normal structure and function of connective tissues. ECM is secreted locally by cells and organized into a complex meshwork providing physical support to cells, tissues, and organs. Initially thought to act only as a scaffold, the ECM is now known to provide a myriad of signals to cells regulating all aspects of their phenotype from morphology to differentiation. Matricellular proteins are a class of ECM related molecules defined through their ability to modulate cell-matrix interactions. Matricellular proteins are expressed at high levels during development, but typically only appear in postnatal tissue in wound repair or disease, where their levels increase substantially. Members of the CCN family, tenascin-C, osteopontin, secreted protein acidic rich in cysteine (SPARC), bone sialoprotein, thrombospondins, and galectins have all been classed as matricellular proteins. Periostin, a 90 kDa secreted homophilic cell adhesion protein, was recently added to matricellular class of proteins based on its expression pattern and function during development as well as in wound repair. Periostin is expressed in connective tissues including the periodontal ligament, tendons, skin and bone, and is also prominent in neoplastic tissues, cardiovascular disease, as well as in connective tissue wound repair. This review will focus on the functional role of periostin in tissue physiology. Fundamentally, it appears that periostin influences cell behaviour as well as collagen fibrillogenesis, and therefore exerts control over the structural and functional properties of connective tissues in both health and disease. Periostin is a novel matricellular protein with close homology to Drosophila fasciclin 1. In this review, the functional role of periostin is discussed in the context of connective tissue physiology, in development, disease, and wound repair.

Fig. 1

Extracellular localization of periostin protein in ECM secreted by human gingival fibroblasts cultured on titanium

Fig. 2

Six-week old periostin knockout C57BL/6 and litter matched wild types were analyzed using microCT imaging. In wild type mice, the molars are well arranged, with healthy periodontal ligament evident in the sagittal view. Periostin knockout mice have significant defects around the bone and periodontal ligaments, particularly in the back molars (arrow, sagittal view). In the coronal view, bone loss is evident in the jaw (arrows) when periostin knockout mice are compared with wild type litter matched controls

Fig. 3

Analysis of the bone volume and mineral content reveals that the loss of periostin influences formation of bone, which is consistent with the findings of Rios et al.

Fig. 4

MicroCT analysis of wild type C57BL/6 and periostin knockout C57BL/6 mice at a scanning distance of 40 μm. Overall skull shape differed between the mice types, and the orbital bones appear to be missing entirely in the periostin knockout (see arrows) which is a characteristic of Marfan’s syndrome