Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells

Xiao Dong Chen, Songtao Shi, Tianshun Xu, Pamela Gehron Robey, Marian F. Young

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Biglycan (bgn) is an extracellular matrix proteoglycan that is enriched in bone and other skeletal connective tissues. Previously, we generated bgn-deficient mice and showed that they developed age-dependent osteopenia. To identify the cellular events that might contribute to this progressive osteoporosis, we measured the number of osteogenic precursors in the bone marrow of normal and mutant mice. The number of colonies, indicative of the colony-forming unit potential of fibroblasts (CFU-F), gradually decreased with age. By 24 weeks of age, colony formation in the bgn knockout (KO) mice was significantly more reduced than that in the wild type (wt) mice. This age-related reduction was consistent with the extensive osteopenia previously shown by X-ray analysis and histological examination of 24-week-old bgn KO mice. Because bgn has been shown previously to bind and regulate transforming growth factor β (TGF-β) activity, we also asked whether this growth factor would affect colony formation. TGF-β treatment significantly increased the size of the wt colonies. In contrast, TGF-β did not significantly influence the size of the bgn colonies. An increase in apoptosis in bgn-deficient bone marrow stromal cells (BMSCs) was observed also. The combination of decreased proliferation and increased apoptosis, if it occurred in vivo, would lead to a deficiency in the generation of mature osteoblasts and would be sufficient to account for the osteopenia developed in the bgn KO mice. The bgn KO mice also were defective in the synthesis of type I collagen messenger RNA (mRNA) and protein. This result supports the suggestion that the composition of the extracellular matrix may be regulated by specific matrix components including bgn.

Original languageEnglish (US)
Pages (from-to)331-340
Number of pages10
JournalJournal of Bone and Mineral Research
Volume17
Issue number2
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Keywords

  • Biglycan
  • Bone marrow stromal cells
  • Collagen
  • Colony-forming unit fibroblastic
  • Osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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