Tricalcium phosphate particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis in amouse osteolysis model.

Abstract

Wear particles-induced inflammatory osteolysis, a major factor of aseptic loosening affects the long-term survival of orthopedic prostheses. Increasing observations have demonstrated that osteocytes, making up over 95% of all the bone cells, is involved in wear particle-induced periprosthetic osteolysis, but its mechanism remains unclear. In the present study, we embedded micro-sized tricalcium phosphate (TCP) particles (30 mg) under the periosteum around the middle suture of the mouse calvaria to establish a calvarial osteolysis model and investigated the biological effects of the particles on calvaria osteocytes in vivo. Results showed that TCP particles induced pyroptosis and activated the NLRP3 inflammasome in calvaria osteocytes, which was confirmed by obvious increases in empty lacunae, protein expressions of speck-like protein containing CARD (ASC), NOD-like receptor protein 3 (NLRP3), cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and resulted in elevated ratios of Casp-1 p20/Casp-1 and interleukin (IL)-1β/pro-IL-1β. Simultaneously, TCP particles enhanced serum levels of lactate dehydrogenase (LDH) and IL-1β. Furthermore, the pyroptotic effect was reversed by the Casp-1 inhibitor VX765 or the NLRP3 inhibitor MCC950. In addition, TCP particles increased the levels of intracellular reactive oxygen species (ROS) and malonaldehyde (MDA), whereas decreased the antioxidant enzyme nuclear factor E2-related factor 2 (Nrf2) level, leading to oxidative stress in calvaria osteocytes; the ROS scavenger N-acetylcysteine (NAC) attenuated these effects of pyroptotic death and the NLPR3 activation triggered by TCP particles. Collectively, our data suggested that TCP particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis, contributing to osteoclastogenesis and periprosthetic osteolysis.

• Authors: Yun Zhang, Ming Yan, Wanting Niu, Hongjiao Mao, Pei Yang, Bingbing Xu, Yonghong Sun
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 107 Pg. 108699 (Jun 2022) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 35305384 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Phosphates
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLR Proteins
• Nlrp3 protein, mouse
• Reactive Oxygen Species
• Caspase 1
• tricalcium phosphate

Topics

• Animals
• Calcium Phosphates
• Caspase 1 (metabolism)
• Inflammasomes (metabolism)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• NLR Proteins (metabolism)
• Osteocytes
• Osteolysis (metabolism)
• Pyroptosis
• Reactive Oxygen Species (metabolism)
• Skull (metabolism)