Modulation of Notch Signaling by Fringe Proteins: Potential Impacts on Osteoclast Differentiation
Faculty Mentor
Dr. Jason Ashley
Presentation Type
Oral Presentation
Start Date
5-7-2025 9:40 AM
End Date
5-7-2025 10:00 AM
Location
PUB 317
Primary Discipline of Presentation
Biology
Abstract
Osteoporosis is characterized by excessive bone resorption and impaired remodeling, leading to increased fracture risk, particularly in postmenopausal women. Current treatments, such as bisphosphonates and denosumab, inhibit osteoclast activity but suppress necessary remodeling, resulting in brittle bones. Modulating Notch signaling offers a promising alternative to reduce bone resorption while preserving physiological remodeling. Notch signaling, mediated by cell-to-cell interactions, regulates osteoclastogenesis and bone remodeling through HES1 target genes. The Fringe family of glycosyltransferases, including Lunatic, Manic, and Radical Fringe, modifies Notch signaling by altering sugar residues on Notch receptors, thereby influencing osteoclast function. To investigate Fringe contribution to osteoclasts, we used retroviral vectors to increase expression of individual Fringe family members in macrophages isolated from mouse bone marrow. Fringe overexpressing cells were differentiated into osteoclasts via treatment with CSF1 and RANKL, two cytokines that are both necessary for osteoclastogenesis. Compared to controls, we found enhanced number and size of osteoclasts as well as increased osteoclast marker biochemical activity with all three Fringe overexpressing groups. Given the recognized role of Fringe proteins as modulators of Notch signaling, future work will investigate sensitivity of Fringe-overexpressing cells via expression quantification of the Notch target gene Hes1 following exposure to Jagged1, a Notch ligand. These findings suggest that Fringe proteins promote osteoclastogenesis highlighting their role in bone remodeling and their potential as therapeutic targets.
Recommended Citation
Boruff, Maxwell Thomas, "Modulation of Notch Signaling by Fringe Proteins: Potential Impacts on Osteoclast Differentiation" (2025). 2025 Symposium. 4.
https://dc.ewu.edu/srcw_2025/op_2025/o1_2025/4
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Modulation of Notch Signaling by Fringe Proteins: Potential Impacts on Osteoclast Differentiation
PUB 317
Osteoporosis is characterized by excessive bone resorption and impaired remodeling, leading to increased fracture risk, particularly in postmenopausal women. Current treatments, such as bisphosphonates and denosumab, inhibit osteoclast activity but suppress necessary remodeling, resulting in brittle bones. Modulating Notch signaling offers a promising alternative to reduce bone resorption while preserving physiological remodeling. Notch signaling, mediated by cell-to-cell interactions, regulates osteoclastogenesis and bone remodeling through HES1 target genes. The Fringe family of glycosyltransferases, including Lunatic, Manic, and Radical Fringe, modifies Notch signaling by altering sugar residues on Notch receptors, thereby influencing osteoclast function. To investigate Fringe contribution to osteoclasts, we used retroviral vectors to increase expression of individual Fringe family members in macrophages isolated from mouse bone marrow. Fringe overexpressing cells were differentiated into osteoclasts via treatment with CSF1 and RANKL, two cytokines that are both necessary for osteoclastogenesis. Compared to controls, we found enhanced number and size of osteoclasts as well as increased osteoclast marker biochemical activity with all three Fringe overexpressing groups. Given the recognized role of Fringe proteins as modulators of Notch signaling, future work will investigate sensitivity of Fringe-overexpressing cells via expression quantification of the Notch target gene Hes1 following exposure to Jagged1, a Notch ligand. These findings suggest that Fringe proteins promote osteoclastogenesis highlighting their role in bone remodeling and their potential as therapeutic targets.
