TY - JOUR
T1 - N-cadherin and cadherin 11 modulate postnatal bone growth and osteoblast differentiation by distinct mechanisms
AU - Di Benedetto, Adriana
AU - Watkins, Marcus
AU - Grimston, Susan
AU - Salazar, Valerie
AU - Donsante, Christine
AU - Mbalaviele, Gabriel
AU - Radice, Glenn L.
AU - Civitelli, Roberto
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
KW - Bone remodeling
KW - Cell-cell adhesion
KW - Osteoblast differentiation
KW - Osteoporosis
UR - http://www.scopus.com/inward/record.url?scp=77955409133&partnerID=8YFLogxK
U2 - 10.1242/jcs.067777
DO - 10.1242/jcs.067777
M3 - Article
C2 - 20605916
AN - SCOPUS:77955409133
SN - 0021-9533
VL - 123
SP - 2640
EP - 2648
JO - Journal of cell science
JF - Journal of cell science
IS - 15
ER -