Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells.
Osteocalcin, also called Bone Gla Protein (BGP), is the most abundant of the non-collagenous proteins of bone produced by osteoblasts. It consists of a single chain of 46-50 amino acids, according to the species, and contains three vitamin K-dependent gamma-carboxyglutamic acid residues (GLA), involved in its binding to calcium and hydroxylapatite. Accumulating evidences suggest its involvement in bone remodeling, its physiological role, however, is still unclear. In this study the adhesion properties and the biological effects of osteocalcin on osteoclasts have been analyzed using as an experimental model, human osteoclast-like cells derived from giant cell tumors of bone (GCT). Osteocalcin promoted adhesion and spreading of these cells, triggering the release of bone sialoprotein (BSP), osteopontin (OPN) and fibronectin (FN), that in turn induced the clustering in focal adhesions of beta 1 and beta 3 integrin chains. Spreading was dependent upon the synthesis of these proteins. In fact, when the cells were incubated in the presence of monensin during the adhesion assay, they still adhered but spreading did not occur, focal adhesions disappeared and BSP, OPN, and FN were accumulated in intracellular granules. Furthermore osteocalcin induced chemotaxis in a dose-dependent manner. The action of BGP on osteoclasts was mediated by an intracellular calcium increase due to release from thapsigargin-sensitive stores. These results provide evidences that BGP exerts a role in the resorption process, inducing intracellular signaling, migration and adhesion, followed by synthesis and secretion of endogenous proteins.
Institut National de la Sante et de la Recherche Medicale Unit 403 Lyon, France.
C
C
Chenu
S
S
Colucci
M
M
Grano
P
P
Zigrino
R
R
Barattolo
G
G
Zambonin
N
N
Baldini
P
P
Vergnaud
P D
PD
Delmas
A Z
AZ
Zallone
D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D005870:Giant Cell Tumors; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000502:physiology; D007700:Kinetics; D015675:Osteocalcin / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D016023:Integrins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D015675:Osteocalcin; D053495:Osteopontin; D002118:Calcium