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| Select HIV Protease Inhibitors Alter Bone and Fat Metabolism In Vitro |
RENU G. JAIN, A. PAYNE, J. M. LENHARD;
GlaxoSmithKline Inc, RTP, NC. |
| Presentation Number: 219 |
| Objective:, To determine if HIV-protease inhibitors (PIs) affect bone resorption, bone formation and adipocyte formation using cultured osteoclasts, osteoblasts and adipocytes, respectively. Methods: Osteoblastic and adipogenic differentiation of human mesenchymal stem cells (hMSC) in the presence of PIs was determined by measuring alkaline phosphatase (ALP) activity and total triglyceride accumulation. Gene expression analyses of osteogenic alkaline phosphatase and adipogenic diglycerol acyl transferase (DGAT) were simultaneously conducted. Osteoclast activity was measured using a rat neonatal calvaria assay. The PIs used were amprenavir (APV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV) at doses between 5-20 micromolar. Results: Data summarized in the table below are expressed as a percentage change compared to control cells treated with vehicle. P values * Conclusion: Simultaneous inhibition of osteogenesis and adipogenesis of hMSC cells suggest a causal link between bone and fat formation. Also, direct effects of PIs on osteoclasts may explain the altered bone mineral density found in some HIV-infected subjects. Not all PIs exhibited the same effects in vitro suggesting that different PIs have distinct effects on bone and fat metabolism |
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