Phenotypic Effects of Biglycan Deficiency Are Linked to Collagen Fibril Abnormalities, Are Synergized by Decorin Deficiency, and Mimic Ehlers-Danlos-Like Changes in Bone and Other Connective Tissues

• DOI: 10.1359/jbmr.2002.17.7.1180
• Publication Date: 2006-04-26T21:20:26Z
• Authors: A. Corsi; T. Xu; X-D. Chen; A. Boyde; J. Liang; M. Mankani; B. Sommer; R. V. Iozzo; I. Eichstetter; P. Gehron Robey; P. Bianco; M. F. Young
• Keywords: Biglycan; Hydroxylysine; Osteopenia; Ehlers–Danlos syndrome; Type I collagen

Abstract Decorin (dcn) and biglycan (bgn), two members of the family small leucine-rich proteoglycans (SLRPs), are predominant expressed in skin bone, respectively. Targeted disruption dcn gene results laxity fragility, whereas bgn reduced skeletal growth bone mass leading to generalized osteopenia, particularly older animals. Here, we report that deficiency leads structural abnormality collagen fibrils dermis, tendon, a “subclinical” cutaneous phenotype with thinning dermis but without overt fragility. A comparative ultrastructural study different tissues from bgn- dcn-deficient mice revealed have similar effects on fibril structure not bone. Ultrastructural phenotypic analysis newly generated bgn/dcn double-knockout (KO) additive synergistic Severe fragility marked osteopenia characterize double-KO animals which progeroid changes observed also skin. reveals complete loss basic geometry emergence “serrated fibril” morphology. The animal mimics directly rare variant human Ehlers-Danlos syndrome (EDS), (reduced hypodermis), concur as result impaired glycosaminoglycan (GAG) linking core proteins. Our data show morphology reminiscent those occurring varied spectrum EDS induced by both mice. an individual SLRP tissue specific, expression gross depends multiple variables including level SLRPs synergisms between (and likely other macromolecules) determining matrix functional properties.