Snail1 controls bone mass by regulating Runx2 and VDR expression during osteoblast differentiation.
Bone undergoes continuous remodelling throughout adult life, and the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts defines the final bone mass. Here we show that Snail1 regulates this balance by controlling osteoblast differentiation. Snail1 is necessary for the early steps of osteoblast development, and it must be downregulated for their final differentiation. At the molecular level, Snail1 controls bone mass by repressing the transcription of both the osteoblast differentiation factor Runx2 and the vitamin D receptor (VDR) genes in osteoblasts. Sustained activation of Snail1 in transgenic mice provokes deficient osteoblast differentiation, which, together with the loss of vitamin D signalling in the bone, also impairs osteoclastogenesis. Indeed, the mineralisation of the bone matrix is severely affected, leading to hypocalcemia-independent osteomalacia. Our data show that the impact of Snail1 activity on the osteoblast population regulates the course of bone cells differentiation and ensures normal bone remodelling.
de Frutos
Cristina A
CA
Instituto de Neurociencias, CSIC-UMH, San Juan de Alicante, Spain.
Dacquin
Romain
R
Vega
Sonia
S
Jurdic
Pierre
P
Machuca-Gayet
Irma
I
Nieto
M Angela
MA
D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010018:Osteomalacia / Q000235:genetics / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D050659:Core Binding Factor Alpha 1 Subunit; D005452:Fluoresceins; D018167:Receptors, Calcitriol; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C007740:fluorexon