Altered wound healing in mice lacking a functional osteopontin gene (spp1).

Journal Article (Journal Article)

Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)- containing glycoprotein encoded by the gene secreted phosphoprotein 1 (spp1). spp1 is expressed during embryogenesis, wound healing, and tumorigenesis; however, its in vivo functions are not well understood. Therefore, OPN null mutant mice were generated by targeted mutagenesis in embryonic stem cells. In OPN mutant mice, embryogenesis occurred normally, and mice were fertile. Since OPN shares receptors with vitronectin (VN), we tested for compensation by creating mice lacking both OPN and VN. The double mutants were also viable, suggesting that other RGD-containing ligands replace the embryonic loss of both proteins. We tested the healing of OPN mutants after skin incisions, where spp1 was upregulated as early as 6 h after wounding. Although the tensile properties of the wounds were unchanged, ultrastructural analysis showed a significantly decreased level of debridement, greater disorganization of matrix, and an alteration of collagen fibrillogenesis leading to small diameter collagen fibrils in the OPN mutant mice. These data indicate a role for OPN in tissue remodeling in vivo, and suggest physiological functions during matrix reorganization after injury.

Full Text

Duke Authors

Cited Authors

  • Liaw, L; Birk, DE; Ballas, CB; Whitsitt, JS; Davidson, JM; Hogan, BL

Published Date

  • April 1, 1998

Published In

Volume / Issue

  • 101 / 7

Start / End Page

  • 1468 - 1478

PubMed ID

  • 9525990

Pubmed Central ID

  • PMC508725

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI2131


  • eng

Conference Location

  • United States