title: N-cadherin and cadherin 11 modulate postnatal bone growth and osteoblast differentiation by distinct mechanisms.
abstract: We have previously shown that targeted expression of a dominant-negative truncated form of N-cadherin (Cdh2) delays acquisition of peak bone mass in mice and retards osteoblast differentiation; whereas deletion of cadherin 11 (Cdh11), another osteoblast cadherin, leads to only modest osteopenia. To determine the specific roles of these two cadherins in the adult skeleton, we generated mice with an osteoblast/osteocyte specific Cdh2 ablation (cKO) and double Cdh2(+/-);Cdh11(-/-) germline mutant mice. Age-dependent osteopenia and smaller diaphyses with decreased bone strength characterize cKO bones. By contrast, Cdh2(+/-);Cdh11(-/-) exhibit severely reduced trabecular bone mass, decreased in vivo bone formation rate, smaller diaphyses and impaired bone strength relative to single Cdh11 null mice. The number of bone marrow immature precursors and osteoprogenitor cells is reduced in both cKO and Cdh2(+/-);Cdh11(-/-) mice, suggesting that N-cadherin is involved in maintenance of the stromal cell precursor pool via the osteoblast. Although Cdh11 is dispensable for postnatal skeletal growth, it favors osteogenesis over adipogenesis. Deletion of either cadherin reduces β-catenin abundance and β-catenin-dependent gene expression, whereas N-cadherin loss disrupts cell-cell adhesion more severely than loss of cadherin 11. Thus, Cdh2 and Cdh11 are crucial regulators of postnatal skeletal growth and bone mass maintenance, serving overlapping, yet distinct, functions in the osteogenic lineage.
authors.affiliation: Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8301, St Louis, MO 63110, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Marcus
authors.initials: M
authors.lastname: Watkins
authors.forename: Susan
authors.initials: S
authors.lastname: Grimston
authors.forename: Valerie
authors.initials: V
authors.lastname: Salazar
authors.forename: Christine
authors.initials: C
authors.lastname: Donsante
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mbalaviele
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Radice
authors.forename: Roberto
authors.initials: R
authors.lastname: Civitelli
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015820:Cadherins; C086960:osteoblast cadherin