Figure 2.

The osteoclast as a target for TDF. A) Bone tissue, osteoblasts and osteoclasts. TDF, as a phosphonate, associates with bone tissue. Bone resorption by osteoclasts would result in the preferential uptake of TDF. B) Impact of TDF on osteoclast DNA synthesis and gene expression. Following TDF uptake by osteoclasts, TDF can target the nucleus (1) and/or mitochondria (2), where it may directly or indirectly perturb DNA synthesis by 1) incorporation and DNA chain termination, 2) DNA damage, 3) alteration of deoxynucleotide transport, and/or 4) nucleotide pool imbalances. The impact of TDF on cellular DNA synthesis would result in altered gene expression (3).

Abbreviation: TDF, tenofovir disoproxil fumarate.