Increased bone resorption and osteopenia in Dlx5 heterozygous mice.
Distal-less (Dlx) homeobox transcription factors play a central role in the control of osteogenesis. In particular, Dlx5 regulates osteoblasts/osteoclasts coupling during perinatal bone formation. We analyze here the effect of Dlx5 allelic reduction in the control of bone remodeling. We first show that Dlx5 expression persists during postnatal bone development. We then compare the skeletal phenotype of 10- and 20-week-old Dlx5(+/-) mice to that of wild-type (WT) littermates. Dlx5(+/-) male mice exhibit lower bone mineral density (BMD) at both ages while only 20-week-old females are affected. microCT analyses reveal a reduction in cortical thickness of femoral midshafts in Dlx5(+/-) mice. Histomorphometry on distal femora shows no changes in trabecular structure and confirms a reduction in Dlx5(+/-) cortical thickness. The cortical decrease of 10-week-old mice does not derive from a reduction in periosteal bone apposition, but results from increased bone resorption with a significantly higher number of endosteal osteoclasts per bone surface and a larger marrow diameter. Urinary level of deoxypyridinoline is also higher in heterozygous mice confirming an increase in bone resorption activity. Our findings might be relevant for understanding complex, multifactorial diseases such as osteoporosis in which quantitative deregulation of gene expression leads to disruption of bone homeostasis.
INSERM U606, Hôpital Lariboisière, 2, rue Ambroise-Paré, 75475 Paris Cedex 10, France.
Nadeem
N
Samee
Valérie
V
Geoffroy
Caroline
C
Marty
Corinne
C
Schiltz
Maxence
M
Vieux-Rochas
Philippe
P
Clément-Lacroix
Cécile
C
Belleville
Giovanni
G
Levi
Marie-Christine
MC
de Vernejoul
D000596:Amino Acids / Q000652:urine; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000150:complications*; D001862:Bone Resorption / Q000150:complications*; D005269:Femur / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006238:Haploidy; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D055114:X-Ray Microtomography; D001616:beta-Galactosidase / Q000378:metabolism
D000596:Amino Acids; D015415:Biomarkers; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; C036020:deoxypyridinoline; D001616:beta-Galactosidase