Fringe Protein Expression Modulates Notch Signaling and Impacts Osteoclastogenesis
Faculty Mentor
Jason Ashley
Presentation Type
Oral Presentation
Start Date
4-14-2026 11:40 AM
End Date
4-14-2026 12:00 PM
Location
PUB 317
Primary Discipline of Presentation
Biology
Abstract
Osteoporosis is characterized by excessive bone resorption and impaired skeletal remodeling, resulting in increased fracture risk, particularly in postmenopausal populations. Current treatments such as bisphosphonates and denosumab suppress osteoclast activity, but prolonged inhibition of remodeling can lead to reduced bone quality. Studies on Notch signaling have emerged as an important regulator of osteoclastogenesis, and its modulation may provide a novel strategy to reduce bone resorption while maintaining bone integrity. There are three members of the Fringe family of glycosyltransferases including Lunatic, Manic, and Radical Fringe, that modify Notch receptors and influence downstream signaling activity. Previous work from our lab demonstrated that overexpression of Fringe proteins in primary bone marrow derived macrophages increased osteoclast size and tartrate resistant acid phosphatase activity. However, primary macrophage cultures are limited by the low cell yields obtained from mouse bone marrow. To overcome this limitation, we utilized the ER-HoxB8 conditional immortalization system to generate a renewable myeloid progenitor population. Our PCR analysis confirmed successful plasmid insertion and overexpression of constructs, but full RNA sequencing will be performed to verify stable transgene expression and characterize downstream transcriptional changes. Currently, we have observed increased osteoclast differentiation associated with elevated Radical Fringe expression and increased resorption. Ongoing studies are assessing actin ring formation and bone resorption using mineralized bone chip assays. These findings could further support the role of Fringe proteins in regulating osteoclastogenesis and highlight their utility in bone remodeling.
Recommended Citation
Boruff, Maxwell, "Fringe Protein Expression Modulates Notch Signaling and Impacts Osteoclastogenesis" (2026). 2026 Symposium. 8.
https://dc.ewu.edu/srcw_2026/op_2026/o1_2026/8
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Fringe Protein Expression Modulates Notch Signaling and Impacts Osteoclastogenesis
PUB 317
Osteoporosis is characterized by excessive bone resorption and impaired skeletal remodeling, resulting in increased fracture risk, particularly in postmenopausal populations. Current treatments such as bisphosphonates and denosumab suppress osteoclast activity, but prolonged inhibition of remodeling can lead to reduced bone quality. Studies on Notch signaling have emerged as an important regulator of osteoclastogenesis, and its modulation may provide a novel strategy to reduce bone resorption while maintaining bone integrity. There are three members of the Fringe family of glycosyltransferases including Lunatic, Manic, and Radical Fringe, that modify Notch receptors and influence downstream signaling activity. Previous work from our lab demonstrated that overexpression of Fringe proteins in primary bone marrow derived macrophages increased osteoclast size and tartrate resistant acid phosphatase activity. However, primary macrophage cultures are limited by the low cell yields obtained from mouse bone marrow. To overcome this limitation, we utilized the ER-HoxB8 conditional immortalization system to generate a renewable myeloid progenitor population. Our PCR analysis confirmed successful plasmid insertion and overexpression of constructs, but full RNA sequencing will be performed to verify stable transgene expression and characterize downstream transcriptional changes. Currently, we have observed increased osteoclast differentiation associated with elevated Radical Fringe expression and increased resorption. Ongoing studies are assessing actin ring formation and bone resorption using mineralized bone chip assays. These findings could further support the role of Fringe proteins in regulating osteoclastogenesis and highlight their utility in bone remodeling.
