Jeanna Schmanski
Pronouns: She/Her/Hers
Research Mentor(s): Kurt Hankenson
Research Mentor School/College/Department: Orthopaedic Surgery / Medicine
Program: UROPF
Session: Session 3 (11:00am – 11:50am)
Authors: Jeanna Schmanski, Christina Capobianco, Kurt Hankenson
Abstract
Non-union fractures take place when a broken or fractured bone does not heal correctly in the expected period, occurring in as many as 20% of all fractures, depending on patient age, comorbidities, fracture site, and other complications[1]. A failure to heal is often brought about by a lack of blood flow to the site of the injury. Under these ischemic conditions, oxygen and nutrients are not sufficiently transported to the cells, causing a delay in recovery. To better understand bone healing, we study thrombospondin 1 (TSP1), a gene involved in the regulation of blood vessel formation that is expressed by mesenchymal-lineage cells[2]. TSP1 is highly expressed during fracture healing and thus could be a molecule that regulates vascularization during the fracture healing process, but TSP1 can also have cell-autonomous effects and influence cell proliferation and differentiation. We performed in vitro experiments using bone marrow-derived mesenchymal progenitor cells (BMSCs) from TSP1-null and wild-type mice to interrogate the role of TSP1 in cell proliferation and osteogenic differentiation, as TSP1 reportedly plays a role in osteogenesis[3]. We have observed differences between wild-type and TSP1 knockout MSCs. TSP1-null MSC have a proliferation deficiency, supporting our hypothesis that the TSP1 pathway has a significant role in fracture healing and callus formation. Ongoing studies have similarly denoted a decrease in the osteogenic potential in the absence of TSP1. Understanding TSP in relation to fracture healing, and why TSP1 knockout mice have reduced fracture callus size, will allow us to better manipulate an ischemic environment to encourage complete healing of non-unions. References: (2023). Pennmedicine.org. https://www.pennmedicine.org/departments-and-centers/orthopaedic-surgery/about-us/excellence-in-motion-newsletter/archive/2019-newsletter/treatment-of-nonunion-and-malunion#:~:text=Despite%20the%20quality%20of%20care Bornstein, P. (2009). Thrombospondins function as regulators of angiogenesis. Journal of Cell Communication and Signaling, 3(3-4), 189–200. https://doi.org/10.1007/s12079-009-0060-8 Bailey DuBose, K., Zayzafoon, M., & Murphy-Ullrich, J. E. (2012). Thrombospondin-1 inhibits osteogenic differentiation of human mesenchymal stem cells through latent TGF-ß activation. Biochemical and Biophysical Research Communications, 422(3), 488–493. https://doi.org/10.1016/j.bbrc.2012.05.020
