Targeting Piezo ion channels for mitigation of osteoarthritis pain and disease progression
Abstract
The purpose of this project is to determine the roles of Piezo mechano-sensing channels in osteoarthritis (OA) and pain associated with OA using mouse genetic models. Two major aims are proposed.1) assessment of the effect of cartilage-specific loss of Piezo1 and Piezo2 in OA progression in surgically created OA in mice, and 2) assessment of OA-associated pain in Piezo2 haplo-insufficient mice. The scope of this project for the first year is generation of mouse modles and validation, optimization of assay system, and surgical procedure for Aim 1 (neuron specific Piezo KO) and Aim 2 (cartilage-specific Piezo KO) to establish and collect essential tools and information for the second year experiments using mice induced with OA byDMM surgery to assess the effect of Piezo deletion in OA and OA-associated pain.Major findings: The progress of the project is unfortunately significantly slowed down due to colony cutdown and the facility shutdown during the pandemic, and therefore we have collected limited amounts of data. We have bred floxed Piezo1 and floxed Piezo2 and Cre transgenic mice to generate breeding mice with cartilagex2;specific and neuron specific Piezo deletion. For Specific Aim 1, we collaborate with the orthopaedic research laboratory at MGH to start testing the feasibility of assessing pain with incapacitance test as well as their gait assessment system using mice received DMM surgery. Unlike reported in a small number of literature, our preliminary data suggest that assessment of mouse OA-associated pain is technically challenging because the changes detected by these assays modest compared with the assay variability. For Specific Aim2, during the first year, we have mainly worked on Major Task3 generating and validating mouse models with cartilage-specific Piezo KO. We have generated and have analyzed the basal phenotype of cartilage-specific Piezo1 knockout mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1129130
Entities
People
- Tatsuya Kobayashi
Organizations
- Massachusetts General Hospital