Effects and mechanisms of microenvironmental acidosis on osteoclast biology

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration

“… 2 The resorption lacuna is acidified due to the release of protons, and this acidification is efficient, reducing the pH to 3 within a few minutes of the resorption space. 7 Moreover, the excess protons return to the cytoplasm, causing periodic pH oscillations within osteoclasts. 7 This pH dynamic has raised questions regarding whether the cytoplasm becomes alkalinized during the proton release into the resorption lacuna.…”

“… 7 Moreover, the excess protons return to the cytoplasm, causing periodic pH oscillations within osteoclasts. 7 This pH dynamic has raised questions regarding whether the cytoplasm becomes alkalinized during the proton release into the resorption lacuna. Recent mathematical models suggest that AE2 plays a role in preventing alkalinization within osteoclasts, even in the face of substantial proton release.…”

“…In turn, some of the released H + is then reabsorbed into the cell from the sealing lacuna, resulting in periodic H + oscillations and gradual cytoplasm acidification. 7 Additionally, specific organelles are acidic, such as endosomes (pH: 4.9–6.0) and lysosomes (pH: 4.0–4.5), which are responsible for endocytosis of nanoparticles into osteoclasts. 8 , 9 This characteristics of acidic microenvironmental of osteoclasts underscores the potential of pH-sensitive gated drug delivery systems as a therapeutic strategy for conditions characterized by excessive bone resorption.…”

Development of a novel cholesterol tag-based system for trans-membrane transport of protein drugs

“…During the development of a novel therapy, we sometimes need to deliver therapeutic proteins or drugs from extracellular fluid to the cytoplasm (6). However, cytosolic delivery of therapeutic proteins is usually hampered by cell membrane obstruction, endocytic sequestration, and lysosomal breakdown, which present notable barriers for approaching those intracellular targets (7)(8)(9). Hence, delivering therapeutic proteins/drugs into the cytoplasm is a challenge during the development of novel strategies to fight against these refractory diseases (10,11).…”