Osteoblast differentiation is impaired in SOCS-1-deficient mice.
The suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible intracellular molecule that inhibits excessive activation of the JAK-STAT-mediated signal cascade initiated by various stimuli. The smaller size of SOCS-1 knockout (KO) mice suggests the presence of skeletal abnormality caused by the disruption of the regulatory system in JAK-STAT signaling. In addition to macroscopic examination, peripheral quantitative computed tomography (pQCT), bone histomorphometrical analysis, and in situ hybridization were used to examine the skeletal properties of SOCS-1 KO mice. Moreover, differentiation of primary cultured osteoblasts was investigated. Distinct phosphorylation of STAT1 was detected in the SOCS-1 KO calvarial cells but was hardly detectable in wild-type (WT) mice. Undercalcified areas in the skulls and sternum, as well as comparatively thinner calcified areas of cortical bone, were found in SOCS-1 KO mice. pQCT analysis showed a marked decrease in salt content, whereas the mineralization activity of primary cultured calvarial cells strongly suggested significant impairment in osteoblasts of SOCS-1 KO mice. In situ hybridization analysis demonstrated that these mice expressed the early markers [type I collagen (COL-1) and osteonectin (ON)] and the mid-marker [osteopontin (OP)] at levels comparable with those seen in WT mice. However, a dramatic decrease was observed in the expression level of the late marker [osteocalcin (OC)] of osteoblasts. Our findings thus demonstrate that SOCS-1 regulates osteoblast differentiation in the later stage.
Abe
Tatsuo
T
Department of Molecular Medicine, Graduate School of Osaka University Medical School, Suita, Japan.
Nomura
Shintaro
S
Nakagawa
Reiko
R
Fujimoto
Minoru
M
Kawase
Ichiro
I
Naka
Tetsuji
T
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics; D012863:Skeleton; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins