Reduced bone mineral density in SOCS-2-deficient mice.
Suppressor of cytokine signaling-2 (SOCS-2) is a member of the suppressor of cytokine signaling family, implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal transduction pathway. We have previously reported that SOCS-2-/- mice display an increased longitudinal skeletal growth associated with a deregulated GH/IGF-I signaling. The aim of the present study was to determine the role of SOCS-2 in the regulation of bone mineral density (BMD). Dual x-ray absorptiometry (DXA) analyses demonstrated that the areal BMD of the tibia was reduced in both 4-wk-old (-8.6%) and 15-wk-old (-6.0%) SOCS 2-/- mice compared with wild-type (WT) mice. The trabecular volumetric BMD, as measured by peripheral quantitative computerized tomography (pQCT) in the metaphyseal region of the distal femur, was reduced in both 4-wk-old (-10%) and 15-wk-old (-32%) SOCS 2-/- mice compared with WT mice. pQCT analyses in the diaphyseal region of tibia also revealed that the cortical volumetric BMD was reduced in both 4-wk-old (-7%) and 15-wk-old (-3%) SOCS 2-/- mice. The cortical cross-sectional area was reduced in 4-wk-old but not in 15-wk-old SOCS 2-/- mice. In conclusion, SOCS-2 inactivation results in reduced trabecular and cortical volumetric BMD. These effects are not consistent with an augmented GH/IGF-I signaling and, therefore, the mechanism behind the reduced BMD remains to be elucidated.
Lorentzon
Mattias
M
Center for Bone Research at the Sahlgrenska Academy, Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg University, 41345 Gothenburg, Sweden. Mattias.Lorentzon@medic.gu.se
Greenhalgh
Chris J
CJ
Mohan
Subburaman
S
Alexander
Warren S
WS
Ohlsson
Claes
C
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005269:Femur / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053613:Janus Kinase 1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015675:Osteocalcin / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1