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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\u2013computed tomographic (\u00b5CT) 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\u2013derived 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. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.118","type":"journal-article","created":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T14:43:25Z","timestamp":1272725005000},"page":"2138-2147","source":"Crossref","is-referenced-by-count":157,"title":["<i>Wnt10b<\/i> deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells"],"prefix":"10.1093","volume":"25","author":[{"given":"Jennifer R","family":"Stevens","sequence":"first","affiliation":[{"name":"Department Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA"},{"name":"Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 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