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

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

  • Eur J Pharmacol. 2024 Mar 15:967:176364. doi: 10.1016/j.ejphar.2024.176364.
Jingmin Che 1,  Xin Chen 2,  Weihao Ren 2,  Peng Shang 3
Affiliations

Affiliations

  • 1 Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, China; Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an, Shaanxi, China. Electronic address: jm.che1123@mail.nwpu.edu.cn.
  • 2 Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, China; School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China; Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
  • 3 Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, China; Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an, Shaanxi, China. Electronic address: shangpeng@nwpu.edu.cn.
PMID: 38316249 DOI: 10.1016/j.ejphar.2024.176364
Abstract

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.

Keywords

Apoptosis; Autophagy; Osteocyte; PTH 1–34; RPM.

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