| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 22, 19247-19250, May 31, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Metabolic Diseases, GlaxoSmithKline Inc.,
Research Triangle Park, North Carolina 27709
Human immunodeficiency virus (HIV) therapies have
been associated with alterations in fat metabolism and bone mineral
density. This study examined the effects of HIV protease inhibitors
(PIs) on bone resorption, bone formation, and adipocyte
differentiation using ex vivo cultured osteoclasts,
osteoblasts, and adipocytes, respectively. Osteoclast activity,
measured using a rat neonatal calvaria assay, increased in the presence
of nelfinavir (NFV; 47.2%, p = 0.001), indinavir
(34.6%, p = 0.001), saquinavir (24.3%, p = 0.001), or ritonavir (18%, p < 0.01). In contrast, lopinavir (LPV) and amprenavir did not increase
osteoclast activity. In human mesenchymal stem cells (hMSCs), the PIs
LPV and NFV decreased osteoblast alkaline phosphatase enzyme activity
and gene expression significantly (p < 0.05). LPV and
NFV diminished calcium deposition and osteoprotegrin expression
(p < 0.05), whereas the other PIs investigated did
not. Adipogenesis of hMSCs was strongly inhibited by saquinavir and NFV
(>50%, p < 0.001) and moderately inhibited by
ritonavir and LPV (>40%, p < 0.01). Expression of
diacylglycerol transferase, a marker of adipocyte differentiation,
decreased in hMSCs treated with NFV. Amprenavir and indinavir did not
affect adipogenesis or lipolysis. These results suggest that bone and fat formation in hMSCs of bone marrow may be coordinately
down-regulated by some but not all PIs.
ACCELERATED PUBLICATION
Select HIV Protease Inhibitors Alter Bone and Fat Metabolism
ex Vivo*
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Metabolic
Diseases, GlaxoSmithKline Inc., 5 Moore Dr., Research Triangle Park, NC
27709. Tel.: 919-483-3022; Fax: 919-483-5691; E-mail: jml29514@gsk.com.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. PAN, Z. YANG, S. W. BALLINGER, and J. M. MCDONALD Pathogenesis of Osteopenia/Osteoporosis Induced by Highly Active Anti-Retroviral Therapy for AIDS Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 297 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Q. Hong-Brown, A. M. Pruznak, R. A. Frost, T. C. Vary, and C. H. Lang Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E382 - E390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Adler-Wailes, H. Liu, F. Ahmad, N. Feng, C. Londos, V. Manganiello, and J. A. Yanovski Effects of the Human Immunodeficiency Virus-Protease Inhibitor, Ritonavir, on Basal and Catecholamine-Stimulated Lipolysis J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3251 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bourlier, A. Zakaroff-Girard, S. De Barros, C. Pizzacalla, V. D. de Saint Front, M. Lafontan, A. Bouloumie, and J. Galitzky Protease Inhibitor Treatments Reveal Specific Involvement of Matrix Metalloproteinase-9 in Human Adipocyte Differentiation J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1272 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vernochet, S. Azoulay, D. Duval, R. Guedj, F. Cottrez, H. Vidal, G. Ailhaud, and C. Dani Human Immunodeficiency Virus Protease Inhibitors Accumulate into Cultured Human Adipocytes and Alter Expression of Adipocytokines J. Biol. Chem., January 21, 2005; 280(3): 2238 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. Brown, M. D. Ruppe, R. Kassner, P. Kumar, T. Kehoe, A. S. Dobs, and J. Timpone Reduced Bone Mineral Density in Human Immunodeficiency Virus-Infected Patients and Its Association with Increased Central Adiposity and Postload Hyperglycemia J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1200 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Arpadi, M. Horlick, and E. Shane Metabolic Bone Disease in Human Immunodeficiency Virus-Infected Children J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 21 - 23. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Fakruddin and J. Laurence HIV Envelope gp120-mediated Regulation of Osteoclastogenesis via Receptor Activator of Nuclear Factor {kappa}B Ligand (RANKL) Secretion and Its Modulation by Certain HIV Protease Inhibitors through Interferon-{gamma}/RANKL Cross-talk J. Biol. Chem., November 28, 2003; 278(48): 48251 - 48258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tran, S. Robinson, I. Mikhailenko, and D. K. Strickland Modulation of the LDL receptor and LRP levels by HIV protease inhibitors J. Lipid Res., October 1, 2003; 44(10): 1859 - 1869. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
