EMAIL THIS PAGE TO A FRIEND

Bone

Partial loss of Smad7 function impairs bone remodeling, osteogenesis and enhances osteoclastogenesis in mice.


PMID 24998669

Abstract

Smad7 is well demonstrated as a negative regulator of TGF-β signaling. Its alteration in expression often results in diseases such as cancer and fibrosis. However, the exact role of Smad7 in regulating bone remodeling during mammalian development has not been properly delineated. In this study we performed experiments to clarify the involvement of Smad7 in regulating osteogenesis and osteoclastogenesis both invivo and invitro. Genetically engineered Smad7(ΔE1) (KO) mice were used, whereby partial functional of Smad7 is lost by deleting exon I of the Smad7 gene and the truncated proteins cause a hypomorphic allele. Analysis with μCT imagery and bone histomorphometry showed that the KO mice had lower TbN, TbTh, higher TbSp in the metaphysic region of the femurs at 6, 12, 24weeks from birth, as well as decreased MAR and increased osteoclast surface compared with the WT mice. In vitro BM-MSC multi-lineage differentiation evaluation showed that the KO group had reduced osteogenic potential, fewer mineralized nodules, lower ALP activity, and reduced gene expression of Col1A1, Runx2 and OCN. The adipogenic potential was elevated in the KO group with more formation of lipid droplets, and increased gene expression of Adipsin and C/EBPα. The osteoclastogenic potential of KO mice BMMs was elevate, with emergence of more osteoclasts, larger resorptive areas, and increased gene expression of TRAP and CTR. Our results indicate that partial loss of Smad7 function in mice leads to compromised bone formation and enhanced bone resorption. Thus, Smad7 is acknowledged as a novel key regulator between osteogenesis and osteoclastogenesis.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB4504210
Anti-phospho-Smad3 (pSer204) antibody produced in rabbit, affinity isolated antibody
SAB4504211
Anti-phospho-Smad3 (pSer208) antibody produced in rabbit, affinity isolated antibody
SAB4504212
Anti-phospho-Smad3 (pSer213) antibody produced in rabbit, affinity isolated antibody
SAB4503781
Anti-phospho-Smad3 (pSer425) antibody produced in rabbit, affinity isolated antibody
SAB4300253
Anti-phospho-SMAD3 (pSer425) antibody produced in rabbit, affinity isolated antibody
SAB4504209
Anti-phospho-Smad3 (pThr179) antibody produced in rabbit, affinity isolated antibody
SAB4200346
Anti-SMAD7 (N-terminal) antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody, western blot: 2 μg/mL
AV32008
Anti-SMAD7 antibody produced in rabbit, affinity isolated antibody
HPA028897
Anti-SMAD7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB4200345
Anti-SMAD7 antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody
WH0004092M5
Monoclonal Anti-SMAD7 antibody produced in mouse, clone 2G6, purified immunoglobulin, buffered aqueous solution
SAB1404041
Monoclonal Anti-SMAD7 antibody produced in mouse, clone 4E1, purified immunoglobulin, buffered aqueous solution
SAB1409297
Monoclonal Anti-SMAD7 antibody produced in mouse, clone 3G8, purified immunoglobulin, buffered aqueous solution