Sclerostin binds and regulates the activity of cysteine-rich protein 61.
Sclerostin, a secreted glycoprotein, regulates osteoblast function. Using yeast two-hybrid and direct protein interaction analyses, we demonstrate that sclerostin binds the Wnt-modulating and Wnt-modulated, extracellular matrix protein, cysteine-rich protein 61 (Cyr61, CCN1), which regulates mesenchymal stem cell proliferation and differentiation, osteoblast and osteoclast function, and angiogenesis. Sclerostin was shown to inhibit Cyr61-mediated fibroblast attachment, and Cyr61 together with sclerostin increases vascular endothelial cell migration and increases osteoblast cell division. The data show that sclerostin binds to and influences the activity of Cyr61.
Craig
Theodore A
TA
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Bhattacharya
Resham
R
Mukhopadhyay
Debabrata
D
Kumar
Rajiv
R
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D005819:Genetic Markers; C422903:SOST protein, human