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Intra- and intermolecular covalent cross-linking between collagen fibrils, catalyzed by lysyl oxidase (LOX), determines the mechanical properties of connective tissues; however, mechanisms that regulate the collagen cross-linking according to tissue specificity are not well understood. Here we show that periostin, a secretory protein in the dense connective tissues, promotes the activation of LOX. Previous studies showed that periostin null mice exhibit reduced collagen cross-linking in their femurs, periosteum, infarcted myocardium, and tendons. Presently, we showed that active LOX protein, formed by cleavage of its propeptide by bone morphogenetic protein-1 (BMP-1), was decreased in calvarial osteoblast cells derived from periostin null mice. Overexpression of periostin promoted the proteolytic cleavage of the propeptide, which increased the amount of active LOX protein. The results of co-immunoprecipitation and solid phase binding assays revealed that periostin interacted with BMP-1. Furthermore, this interaction probably resulted in enhanced deposition of BMP-1 on the extracellular matrix, suggesting that this enhanced deposition would lead to cleavage of the propeptide of LOX. Thus, we demonstrated that periostin supported BMP-1-mediated proteolytic activation of LOX on the extracellular matrix, which promoted collagen cross-linking.

Pulmonary capillary leakage followed by influx of blood fluid into the air space of lung alveoli is a crucial step in the progression of acute lung injury (ALI). This influx is due to increased permeability of the alveolar–capillary barrier. The extracellular matrix (ECM) between the capillary and the epithelium would be expected to be involved in prevention of the influx; however, the role of the ECM remains to be addressed. Here, we show that the ECM architecture organized by periostin, a matricellular protein, plays a pivotal role in the survival of bleomycin-exposed mice. Periostin was localized in the alveolar walls. Although periostin-null mice displayed no significant difference in lung histology and air–blood permeability, they exhibited early lethality in a model of bleomycin-induced lung injury, compared with their wild-type counterparts. This early lethality may have been due to increased pulmonary leakage of blood fluid into the air space in the bleomycin-exposed periostin-null mice. These results suggest that periostin in the ECM architecture prevents pulmonary leakage of blood fluid, thus increasing the survival rate in mice with ALI. Thus, this study provides an evidence for the protective role of the ECM architecture in the lung alveoli. [ABSTRACT FROM AUTHOR]

Abstract: A characteristic tooth of rodents, the incisor continuously grows throughout life by the constant formation of dentin and enamel. Continuous eruption of the incisor is accompanied with formation of shear zone, in which the periodontal ligament is remodeled. Although the shear zone plays a role in the remodeling, its molecular biological aspect is barely understood. Here, we show that periostin is essential for formation of the shear zone. Periostin −/− mice showed an eruption disturbance of incisors. Histological observation revealed that deletion of periostin led to disappearance of the shear zone. Electron microscopy revealed that the disappearance of the shear zone resulted from a failure in digestion of collagen fibers in the periostin −/− mice. Furthermore, immunohistochemical analysis using anti-periostin antibodies demonstrated the restricted localization of periostin protein in the shear zone. Periostin is an extracellular matrix protein, and immunoelectron microscopy showed a close association of periostin with collagen fibrils in vivo. These results suggest that periostin functions in the remodeling of collagen matrix in the shear zone. [Copyright &y& Elsevier]