A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations.
Upon removal of its sialic acid or galactose residue, vitamin D-binding protein (DBP) becomes a potent macrophage-activating factor, DBP-MAF. Here we document a new function of DBP-MAF and its parent molecule, DBP, in osteoclast control. We show that all DBPs potently inhibit extracellular Ca2+ (cation) sensing at low nanomolar concentrations with the following rank order of potency: native DBP = sialidase-treated DBP > beta-galactosidase-treated DBP. This attenuation remains unaffected despite co-incubation either with the native DBP ligand, 1,25-dihydroxyvitamin D3, or with an asialoglycoprotein receptor modulator, asialoorosomucoid. Taken together, the results suggest that circulating DBP may play a role in the systemic control of osteoclastic bone resorption, a hitherto unrecognized action of the protein.
Adebanjo
O A
OA
Center for Osteoporosis and Skeletal Aging, Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
Moonga
B S
BS
Haddad
J G
JG
Huang
C L
CL
Zaidi
M
M
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000494:pharmacology; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D016215:Macrophage-Activating Factors / Q000737:chemistry / Q000378:metabolism; D009439:Neuraminidase; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D001616:beta-Galactosidase
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D016215:Macrophage-Activating Factors; D009961:Orosomucoid; D011956:Receptors, Cell Surface; D014809:Vitamin D-Binding Protein; C017030:asialoorosomucoid; C101908:vitamin D-binding protein-macrophage activating factor; D009439:Neuraminidase; D001616:beta-Galactosidase; D002117:Calcitriol; D002118:Calcium