Stimulation of chondrocyte hypertrophy by chemokine stromal cell-derived factor 1 in the chondro-osseous junction during endochondral bone formation.
During endochondral bone formation, chondrocytes undergo differentiation toward hypertrophy before they are replaced by bone and bone marrow. In this study, we found that a G-protein coupled receptor CXCR4 is predominantly expressed in hypertrophic chondrocytes, while its ligand, chemokine stromal cell-derived factor 1 (SDF-1) is expressed in the bone marrow adjacent to hypertrophic chondrocytes. Thus, they are expressed in a complementary pattern in the chondro-osseous junction of the growth plate. Transfection of a CXCR4 cDNA into pre-hypertrophic chondrocytes results in a dose-dependent increase of hypertrophic markers including Runx2, Col X, and MMP-13 in response to SDF-1 treatment. In organ culture SDF-1 infiltrates cartilage and accelerates growth plate hypertrophy. Furthermore, a continuous infusion of SDF-1 into the rabbit proximal tibial physis results in early physeal closure, which is accompanied by a transient elevation of type X collagen expression. Blocking SDF-1/CXCR4 interaction suppresses the expression of Runx2. Thus, interaction of SDF-1 and CXCR4 is required for Runx2 expression. Interestingly, knocking down Runx2 gene expression results in a decrease of CXCR4 mRNA levels in hypertrophic chondrocytes. This suggests a positive feedback loop of stimulation of chondrocyte hypertrophy by SDF-1/CXCR4, which is mediated by Runx2.
Wei
Lei
L
Department of Orthopaedics, The Warren Alpert Medical School of Brown University/Rhode Island Hospital, Suite 402A, 1 Hoppin Street, Providence RI 02903, USA. Lei_Wei@brown.edu
Kanbe
Katsuaki
K
Lee
Mark
M
Wei
Xiaochun
X
Pei
Ming
M
Sun
Xiaojuan
X
Terek
Richard
R
Chen
Qian
Q
D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism*; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005246:Feedback; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D011817:Rabbits; D019718:Receptors, CXCR4 / Q000378:metabolism; D013977:Tibia / Q000378:metabolism
D054377:Chemokine CXCL12; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D019718:Receptors, CXCR4; D053509:Matrix Metalloproteinase 13