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Journal of Histochemistry and Cytochemistry, Vol. 50, 1-10, January 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

SPARC-null Mice Exhibit Accelerated Cutaneous Wound Closure

Amy D. Bradshawa, May J. Reedb, and E. Helene Sagea
a Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington
b Department of Medicine, University of Washington, Seattle, Washington

Correspondence to: E. Helene Sage, The Hope Heart Institute, 1124 Columbia St./Ste. 720, Seattle, WA 98104.

Expression of SPARC (secreted protein acidic and rich in cysteine; osteonectin, BM-40), an extracellular matrix (ECM) associated protein, is coincident with matrix remodeling. To further identify the functions of SPARC in vivo, we have made excisional wounds on the dorsa of SPARC-null and wild-type mice and monitored closure over time. A significant decrease in the size of the SPARC-null wounds, in comparison to that of wild-type, was observed at Day 4 and was maximal at Day 7. Although substantial differences in the percentage of proliferating cells were not apparent in SPARC-null relative to wild-type wounds, primary cultures of SPARC-null dermal fibroblasts displayed accelerated migration, relative to wild-type fibroblasts, in wound assays in vitro. Although the expression of collagen I mRNA in wounds, as measured by in situ hybridization (ISH), was not significantly different in SPARC-null vs wild-type mice, the collagen content of unwounded skin appeared to be substantially lower in the SPARC-null animals. By hydroxyproline analysis, the concentration of collagen in SPARC-null skin was found to be half that of wild-type skin. Moreover, we found an inverse correlation between the efficiency of collagen gel contraction by dermal fibroblasts and the concentration of collagen within the gel itself. We propose that the accelerated wound closure seen in SPARC-null dermis results from its decreased collagen content, a condition contributing to enhanced contractibility. (J Histochem Cytochem 50:1–10, 2002)

Key Words: SPARC, matricellular, transgenic, wound healing, extracellular matrix, collagen


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