RRC ID 54698
Author Kim H, Choi YJ, Lee YS, Park SY, Baek JE, Kim HK, Kim BJ, Lee SH, Koh JM.
Title SLIT3 regulates endochondral ossification by β-catenin suppression in chondrocytes.
Journal Biochem Biophys Res Commun
Abstract Previously, we noted that SLIT3, slit guidance ligand 3, had an osteoprotective role with bone formation stimulation and bone resorption suppression. Additionally, we found that global Slit3 KO mice had smaller long bone. Skeletal staining showed short mineralized length in the newborn KO mice and wide hypertrophic chondrocyte area in the embryo KO mice, suggesting delayed chondrocyte maturation. The recombinant SLIT3 did not cause any change in proliferation of ATDC5 cells, but stimulated expressions of chondrocyte differentiation markers, such as COL2A1, SOX9, COL10A1, VEGF, and MMP13 in the cells. SLIT3 suppressed β-catenin activity in the cells, and activation of Wnt/β-catenin signaling by lithium chloride attenuated the SLIT3-stimulated differentiation markers. ATDC5 cells expressed only ROBO2 among their 4 isotypes, and the Robo2 knock-down with its siRNA reversed the SLIT3-stimulated differentiated markers in chondrocytes. Taken together, these indicate that SLIT3/ROBO2 promotes chondrocyte maturation via the inhibition of β-catenin signaling.
Volume 506(4)
Pages 847-853
Published 2018-12-2
DOI 10.1016/j.bbrc.2018.10.167
PII S0006-291X(18)32351-9
PMID 30389141
MeSH Animals Animals, Newborn Bone and Bones / metabolism Cell Differentiation / drug effects Cell Line Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / drug effects Embryo, Mammalian / metabolism Membrane Proteins / deficiency Membrane Proteins / metabolism* Mice, Knockout Osteogenesis* / drug effects Phenotype Receptors, Immunologic / metabolism Recombinant Proteins / pharmacology beta Catenin / metabolism*
IF 2.705
Times Cited 5
Human and Animal Cells ATDC5(RCB0565)