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Osteoclastogenesis Increased in Pbmcs in Presence of Azt. Presence of Azt Results in Mitochondrial Toxicity But Is Reversed by Application of Rankl
Osteoclastogenesis Increased in Pbmcs in Presence of Azt. Presence of Azt Results in Mitochondrial Toxicity But Is Reversed by Application of Rankl
• (B) Aconitase activity of cell lysates • Over-production of TRAP-positive osteoclasts leads to bone disease.
from RAW264.7 cells treated as
indicated for 3 days • PBMC test results support the conclusion that HIV infection does not
itself accelerate osteoclastogenesis or the effect of AZT in vitro.
• (C) Western blot for mitochondrial
Figure 1: Osteoclastogenic effects by AZT SOD in RAW264.7 cells treated as • AZT induces mtDNA damage while RANKL treatment completely
indicated [for 1–3 days].
(Zidovudine) in RAW264.7 cells are reverses mtDNA damage associated with AZT treatment.
apparent.
• Since increased RANKL levels minimize the deleterious effects of
(A) RAW264.7 cells were treated with AZT at
NRTIs on osteoclast mitochondria, it is possible that they promote
various concentrations in the presence of 50 ng/mL Figure 3: Presence of AZT decreases bone marrow density osteopenia/osteoporosis.
RANKL for 3 days. TRAP staining assay gave an
(BMD) and increases number and surface of osteoblasts.
osteoclast measurement, as shown in the graph. Mice, 5 months old, were orally fed PBS (n = 6, control) or AZT (n 5, AZT 100 • The osteoclastogenic effect of AZT requires the presence of RANKL.
mg/kg/day) for 30 days. Thus, interrupting RANKL by OPG, RANK-Fc, or other compounds
(B) For 1 to 3 days, RAW264.7 cells were treated • BMD measured by DEXA. may be potent therapeutic options.
with RANKL (50 ng/mL, R) or RANKL plus AZT • Histomorphometry was analyzed in three vertebrae of each animal. Osteoclast References:
Pan, George. "Pathogenesis of Osteopenia/Osteoporosis Induced by Highly Active Anti-Retroviral Therapy for
(25 μM, R + A) and total mRNAs were isolated. parameters included number (OcN) and surface (OcS) of osteoclasts. AIDS." Ann N Y Acad Sci. Author manuscript. 1068. (2006): 297-308. Print.
Reported as percentage change using AZT from control.
Pisani, Elizabeth. The Wisdom of Whores. New York: W. W. Norton & Co. Inc., 2008. Print.