PTH 1-34 reduced apoptosis of MLO-Y4 osteocyte-like cells by activating autophagy and inhibiting ER stress under RPM conditions

Osteocytes, as mechanosensitive cells residing within bone tissue, hold a pivotal role in averting the occurrence and progression of osteoporosis. The apoptosis of osteocytes induced by unloading is one of the contributing factors to osteoporosis, although the underlying molecular mechanisms have not been fully elucidated. PTH 1-34 is known to promote bone formation and inhibit bone loss by targeting osteoblasts and osteocytes. However, it is not known whether PTH 1-34 can inhibit osteocyte apoptosis under unloading conditions and the molecular mechanisms involved. In this study, we employed a Random Positioning Machine (RPM) to emulate unloading conditions and cultured MLO-Y4 osteocyte-like cells, in order to unravel the mechanisms through which PTH 1-34 constrains osteocyte apoptosis amidst unloading circumstances. Our findings revealed that PTH 1-34 activated autophagy while suppressing endoplasmic reticulum stress by curtailing the generation of reactive oxygen species (ROS) in MLO-Y4 osteocyte-like cells during unloading conditions. By shedding light on the osteoporosis triggered by skeletal unloading, this study contributes vital insights that may pave the way for the development of pharmacological interventions.