Meredyth Bowman
Pronouns: she/her
Research Mentor(s): Andrea Alford
Co-Presenter:
Research Mentor School/College/Department: Orthopaedic Surgery / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Meredyth Bowman, Anita Reddy, Andrea Alford
Presenter: 9
Abstract
Thrombospondins 1 and 2 (TSP1 and TSP2) are extracellular matrix proteins found in bone. They facilitate collagen fibrillogenesis and bone tissue formation, affect osteoblast differentiation, and could possibly affect osteoblast to osteocyte differentiation. The Alford lab previously conducted proteomic analysis on bones from normal, TSP1-deficient, TSP2-deficient, and TSP1-TSP2 double deficient (DKO) mice. One finding was that sclerostin levels were reduced and beta-catenin levels were elevated in the TSP1-TSP2 DKO bones. Sclerostin is secreted by osteocytes embedded in the bone matrix, and it inhibits bone formation by inhibiting wnt-beta catenin signaling in osteoblasts. The purpose of this project is to confirm and extend the preliminary proteomics data suggesting reduced sclerostin in DKO bone. We hypothesize that TSP1 and TSP2 promote sclerostin expression by osteocytes and thereby limit bone matrix production by osteoblasts. Western blotting will be used to detect sclerostin, as well as type I collagen (a major component of bone matrix) in protein extracts obtained from bones of wild-type and TSP-deficient mice. Band intensities will be determined by densitometry. Sclerostin and type I collagen values will be normalized to those of beta-actin. We anticipate that, compared to the single knockouts, sclerostin levels will be reduced in DKO bones. We also anticipate that bone type I collagen levels will be elevated as a result of the reduction in sclerostin, a negative regulator of bone formation. Successful completion of this research project will tell us about the ways in which thrombospondins present in the bone matrix regulate osteoblast differentiation. More broadly, studying these bone extracellular matrix proteins, can tell us about bone quality, which speaks to fracture risk and overall bone health– especially as we age. The potential increase in the knowledge base could allow the discovery and development of novel treatments for bone fragility.
Biomedical Sciences, Natural/Life Sciences
