Neuro-hormonal control of bone metabolism: vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules

Authors
Lundberg, P Bostrom, I Mukohyama, H Bjurholm, A Smans, K Lerner, UH
Citation
P. Lundberg et al., Neuro-hormonal control of bone metabolism: vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules, REGUL PEPT, 85(1), 1999, pp. 47-58
Citations number
50
Categorie Soggetti
Physiology
Journal title
REGULATORY PEPTIDES
ISSN journal
01670115 → ACNP
Volume
85
Issue
1
Year of publication
1999
Pages
47 - 58
Database
ISI
SICI code
0167-0115(19991130)85:1<47:NCOBMV>2.0.ZU;2-E
Abstract
Based upon the immunohistochemical demonstration of neuropeptides in the sk eleton, including vasoactive intestinal peptide (VIP), we have addressed th e question of whether neuropeptides may exert regulatory roles on bone tiss ue metabolism or not. In the present communication, we have investigated if VIP can affect anabolic processes in osteoblasts, Osteoblasts were isolate d from neonatal mouse calvariae by time sequential enzyme-digestion and sub sequently cultured for 2-28 days in the presence of VIP and other modulator s of cyclic AMP formation. VIP(10(-6) M) stimulated ALP activity and calciu m content. The cyclic AMP phosphodiesterase inhibitors ZK 62 711 (10(-4) M) and isobutyl-methylxanthine (10(-4) M) stimulated ALP activity and synergi stically potentiated the effect of VIP. Neither VIP, nor isobutyl-methylxan thine or ZK 62 711, in the absence or presence of VIP, affected cell number . The stimulatory effect of VIP on ALP activity, in the presence of ZK 62 7 11, was dependent on time and concentration of VIP. The stimulatory effects of VIP and ZK 62 711 on ALP activity was seen also in cells stained for AL P VIP (10(-6) M), in the presence of ZK 62 711 (10-6 M), significantly enha nced mRNA for tissue non-specific ALP. VIP (10(-6) M), in the presence of Z K 62 711, stimulated cyclic AMP production. Forskolin and choleratoxin stim ulated ALP activity and cyclic AMP formation in a concentration-dependent m anner, without affecting cell number. VIP (10(-6) M) and ZK 62 711 (10(-5) M) stimulated, and their combination synergistically enhanced, calcium cont ent in bone noduli. These data show that VIP, without affecting cell prolif eration, can stimulate osteoblastic ALP biosynthesis and bone noduli format ion by a mechanism mediated by cyclic AMP. Our observations suggest a possi bility that anabolic processes in bone are under neurohormonal control. (C) 1999 Elsevier Science B.V. All rights reserved.