2. Academic Validation
  3. Major vault protein (MVP) suppresses aging- and estrogen deficiency-related bone loss through Fas-mediated apoptosis in osteoclasts

Major vault protein (MVP) suppresses aging- and estrogen deficiency-related bone loss through Fas-mediated apoptosis in osteoclasts

  • Cell Death Dis. 2023 Sep 13;14(9):604. doi: 10.1038/s41419-023-05928-4.
Ruobing Wang 1 2,  Yan Yang 1 2,  Zhongyin Zhang 1 2,  Na Zhao 1 2,  Erik A C Wiemer 3,  Jingjing Ben 4,  Junqing Ma 5 6,  Lichan Yuan 7 8
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
  • 2 Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
  • 3 Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • 4 Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
  • 5 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. majunq@163.com.
  • 6 Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. majunq@163.com.
  • 7 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. yuanlichan@njmu.edu.cn.
  • 8 Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. yuanlichan@njmu.edu.cn.
PMID: 37704623 DOI: 10.1038/s41419-023-05928-4
Abstract

Osteoclasts (OCs), derived from monocyte/macrophage lineage, are key orchestrators in bone remodeling. Targeting osteoclast Apoptosis is a promising approach to cut down excessive osteoclast numbers, and thus slow down the rate of bone mass loss that inevitably occurs during aging. However, the therapeutic target of Apoptosis in osteoclasts has not been fully studied. Our previous work generated Mvpf/fLyz2-Cre mice, conditionally depleting major vault protein (MVP) in monocyte lineage, and identified MVP as a bone protector for its negative role in osteoclastogenesis in vivo and in vitro. Here, we observed a notable decline of MVP in osteoclasts with aging in mice, encouraging us to further investigate the regulatory role of osteoclast MVP. Then, Mvpf/fLyz2-Cre mice were exploited in two osteoporosis contexts, aging and abrupt loss of estrogen, and we revealed that conditional knockout of MVP inhibited osteoclast Apoptosis in vivo and in vitro. Moreover, we reported the interaction between MVP and death receptor Fas, and MVP-Fas signaling cascade was identified to positively regulate the Apoptosis of osteoclasts, thus preventing osteoporosis. Collectively, our comprehensive discovery of MVP's regulatory role in osteoclasts provides new insight into osteoclast biology and therapeutic targets for osteoporosis.

Figures
Products