periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype

Abstract

Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (peri lacZ ) embryos are grossly normal. Postnatally, however, ϳ14% of the nulls die before weaning and all of the remaining peri lacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the peri lacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses.

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

“…Recapitulating previous observations (Oshima et al, 2002; Rios et al, 2005), Postn ‐KO mice displayed significantly reduced body weight as well as body and tibia lengths (Figure 2c–e). AT depots displayed no size differences implying that a reduction in periostin does not affect AT development (Figure 2f,g).…”

“…This deletion resulted in decreased body size but did not impair the development of BAT or WAT depots. Our data are thus consistent with previous reports on the role of periostin in bone formation (Rios et al, 2005). While adipose tissue appeared normal under basal conditions, short‐term cold exposure revealed a defective capacity for thermoregulation.…”

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

“…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 2005 Fig . 4 MicroCT analysis of wild type C57BL/6 and periostin knockout C57BL/6 mice at a scanning distance of 40 μm.…”

“…However, with the derivation of the periostin knockout mouse model (Kii et al 2006;Rios et al 2005), the functions of periostin in development, wound repair, and disease, are beginning to be revealed.…”

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

“…It is now generally accepted that tumour cells modify the composition of the adjacent stroma by secreting their own extracellular matrix proteins to create a permissive and supportive environment for their growth (Bissell and Radisky, 2001;Koninger et al, 2004). This hypothesis is supported by the observation that periostin transcription is upregulated in pulmonary smooth muscle cells exposed to hypoxic conditions (Li et al, 2004), in damaged myocardial tissues where migration and resistance of cells to apoptosis is essential (Lindner et al, 2005;Litvin et al, 2005) and in the area around developing teeth where intense cell traction and cell stress occur (Rios et al, 2005). Altogether, these data demonstrate that gain of adhesive interaction induced by overexpression of periostin through the desmoplastic stroma should confer to the cancer cells a selective advantage during the metastatic process and suggest that periostin could be considered as a new member of the matricellular family.…”