Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells

Jennifer R. Stevens, Gustavo Miranda-Carboni, Meredith A. Singer, Sean M. Brugger, Karen M. Lyons, Timothy F. Lane

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Wnt10b is a canonical Wnt ligand expressed in developing bone and has been linked to mesenchymal progenitor functions in mice and humans. Because Wnt signaling has been shown to play an important role in progenitor maintenance in a variety of adult tissues, we examined bone deposition and growth rates throughout postnatal development in Wnt10b-null mice. Using bone histomorphometry and micro-computed tomographic (mCT) studies, we demonstrate that trabecular bone deposition is slightly enhanced in Wnt10b-null mice at 1 month of age, followed by progressive loss with age. Importantly, we find that Wnt10b is required for maintenance of adult bone density in multiple backgrounds of inbred mice and that both copies of the Wnt10b gene are required to maintain normal bone density in 6-month-old animals. We go on to show that the loss in trabecular bone in Wnt10b-null mice is associated with a reduction in the number of bone marrow-derived mesenchymal progenitors (MPCs) using in vitro colony-forming unit assays and marker analysis. Analysis of osteogenic gene expression in primary bone marrow stromal cells demonstrated reductions in expression of several osteoblast differentiation markers. Taken together, our results indicate that Wnt10b is uniquely required for maintenance of mesenchymal progenitor activity in adult bone. The results show the significance of studying individual Wnt ligands and their potentially unique contribution in the context of aging and disease.

Original languageEnglish (US)
Pages (from-to)2138-2147
Number of pages10
JournalJournal of Bone and Mineral Research
Volume25
Issue number10
DOIs
StatePublished - Oct 1 2010

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Mesenchymal Stromal Cells
Bone and Bones
Maintenance
Bone Density
Colony-Forming Units Assay
Ligands
Bone Development
Differentiation Antigens
Osteoblasts
Bone Marrow
Gene Expression
Genes
Cancellous Bone

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells. / Stevens, Jennifer R.; Miranda-Carboni, Gustavo; Singer, Meredith A.; Brugger, Sean M.; Lyons, Karen M.; Lane, Timothy F.

In: Journal of Bone and Mineral Research, Vol. 25, No. 10, 01.10.2010, p. 2138-2147.

Research output: Contribution to journalArticle

Stevens, Jennifer R. ; Miranda-Carboni, Gustavo ; Singer, Meredith A. ; Brugger, Sean M. ; Lyons, Karen M. ; Lane, Timothy F. / Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 10. pp. 2138-2147.
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