RRC ID 37725
Author Macrae VE, Horvat S, Pells SC, Dale H, Collinson RS, Pitsillides AA, Ahmed SF, Farquharson C.
Title Increased bone mass, altered trabecular architecture and modified growth plate organization in the growing skeleton of SOCS2 deficient mice.
Journal J Cell Physiol
Abstract Suppressor of cytokine signalling-2 (SOCS2) negatively regulates the signal transduction of several cytokines. Socs2(-/-) mice show increased longitudinal skeletal growth associated with deregulated GH/IGF-1 signalling. The present study examined the role of SOCS2 in endochondral ossification and trabecular and cortical bone formation, and investigated whether pro-inflammatory cytokines associated with pediatric chronic inflammatory disorders mediate their effects through SOCS2. Seven-week-old Socs2(-/-) mice were heavier (27%; P < 0.001) and longer (6%; P < 0.001) than wild-type mice. Socs2(-/-) tibiae were longer (8%; P < 0.001) and broader (18%; P < 0.001) than that of wild-type mice, and the Socs2(-/-) mice had wider growth plates (24%; P < 0.001) with wider proliferative and hypertrophic zones (10% (P < 0.05) and 14% (P < 0.001) respectively). Socs2(-/-) mice showed increased total cross-sectional bone area (16%: P < 0.001), coupled to increased total tissue area (17%; P < 0.05) compared to tibia from wild-type mice. Socs2(-/-) mice showed increased percent bone volume (101%; P < 0.001), trabecular number (82%; P < 0.001) and trabecular thickness (11%; P < 0.001), with associated decreases in trabecular separation (19%; P < 0.001). TNFalpha exposure to growth plate chondrocytes for 48 h increased SOCS2 protein expression. Growth of metatarsals from 1-day-old Socs2(-/-) and Socs2(+/+) mice, as well as expression of Aggrecan, Collagen Type II and Collagen Type X, were inhibited by TNFalpha, with no effect of genotype. Our data indicate that physiological levels of SOCS2 negatively regulate bone formation and endochondral growth. Our results further suggest that pro-inflammatory cytokines mediate their inhibitory effects on longitudinal bone growth through a mechanism that is independent of SOCS2.
Volume 218(2)
Pages 276-84
Published 2009-2-1
DOI 10.1002/jcp.21593
PMID 18803233
MeSH Animals Animals, Newborn Biomarkers / metabolism Bone Development* / drug effects Bone Resorption / metabolism Cell Proliferation / drug effects Cells, Cultured Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Cytokines / pharmacology Female Gene Expression Regulation Growth Plate / cytology Growth Plate / drug effects Growth Plate / metabolism* Inflammation Mediators / pharmacology Metatarsal Bones / cytology Mice Organ Size / drug effects Osteogenesis / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Suppressor of Cytokine Signaling Proteins / deficiency* Suppressor of Cytokine Signaling Proteins / genetics Suppressor of Cytokine Signaling Proteins / metabolism Tibia / drug effects Tibia / growth & development* Tibia / metabolism
IF 5.546
Times Cited 30
Human and Animal Cells ATDC5(RCB0565)