Tissue crosstalk in joint injury – UROP Spring Symposium 2021

Tissue crosstalk in joint injury

Rida Pervez

Rida Pervez

Pronouns: She/her

Research Mentor(s): Tristan Maerz, Assistant Professor
Research Mentor School/College/Department: Orthopaedic Surgery, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 6 (4pm-4:50pm)
Breakout Room: Room 12
Presenter: 7

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Abstract

Post-traumatic osteoarthritis (PTOA) is a debilitating disease that develops as a result of a joint injury. Overactivation of the Wnt signaling pathway has been implicated in progression of PTOA, however very little is known about this. This work is among the first to study Wnt signaling mechanisms in PTOA. R-spondin 2 is a secreted matricellular protein that functions as an agonist for the Wnt pathway, promoting Wnt signaling. Our preliminary data show that R-spondin 2 is greatly induced in the synovium in a mouse model of PTOA. We also showed that R-spondin 2 is secreted into the synovial fluid after joint injury. This deregulation of R-spondin 2 promotes over-stimulation of the Wnt pathway, which we hypothesize is an important mechanism in joint deterioration. Our aims are to understand the cellular and molecular mechanisms underlying R-spondin 2 and Wnt signaling in PTOA, and how we can manipulate these to inhibit further joint degeneration. To study gene expression in joint-resident cell types, we first analyzed bone marrow stromal cells – primary cells cultured from mice and differentiated into osteoblasts, a cell type present in the joint and relevant to PTOA progression. We isolated RNA, converted it to cDNA, and performed qPCR to analyze gene expression. In parallel, we employed microscopy to study joint pathology over the course of PTOA. Further investigation is now warranted, from which we hope to better understand the cellular and molecular mechanisms of Wnt signaling in PTOA, with the ultimate goal of developing novel therapeutics for treating PTOA.

Authors: Rida Pervez, Alexander Knights, Tristan Maerz
Research Method: Laboratory Research

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