Sexually-divergent differentiation and inflammatory response of osteoclast precursors
Faculty Mentor
Jason Ashley
Document Type
Poster
Start Date
10-5-2023 9:00 AM
End Date
10-5-2023 10:45 AM
Location
PUB NCR
Department
Biology
Abstract
Osteoporosis is an inflammatory degenerative bone disease defined by the decrease in bone density resulting in an increased risk of fracture. Overactivity of osteoclasts, cells responsible for the breakdown of bone matrix, is a defining factor of osteoporosis. Previous studies found lipopolysaccharide (LPS), an inflammatory stimulus associated with bacterial infections, produces larger osteoclast in female derived precursor cells than in male derived cells. Cells that display a higher expression of the Toll-Like Receptor (TLR) signaling pathway are positively correlated to the larger osteoclasts in the female-derived committed osteoclast precursors.
The purpose of this study is to investigate sexually-divergent responses to three inflammatory signals (LPS, zymosan, and double-stranded RNA) in naïve and committed osteoclast precursors with respect to osteoclast differentiation, induction of osteoclast and inflammatory genes, and production of the inflammatory cytokine TNF.
Primary cell cultures of macrophages are harvested from mouse femurs and tibia. Macrophages are pre-exposed to receptor activator of nuclear factor kappa-Β ligand (RANKL) followed by three concentrations of LPS, zymosan and polyinosinic:polycytidylic acid (PolyI:C). Morphological assays are done using fluorescent microscopy. Genetic analysis is done using real-time quantitative polymerase chain reaction (RT-qPCR), and immune responses using enzyme linked immunoassay (ELISA). Preliminary results suggest that all three inflammatory signals can support the differentiation of osteoclast precursors. Future work will quantify and compare differentiation of osteoclasts under these conditions and ascertain whether female and male-derived cells exhibit altered sensitivity to these signals. Completion of this study may enhance mechanistic understanding of sex as a risk variable for bone loss.
Recommended Citation
Cummings, Lilijanna, "Sexually-divergent differentiation and inflammatory response of osteoclast precursors" (2023). 2023 Symposium. 16.
https://dc.ewu.edu/srcw_2023/res_2023/p1_2023/16
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Sexually-divergent differentiation and inflammatory response of osteoclast precursors
PUB NCR
Osteoporosis is an inflammatory degenerative bone disease defined by the decrease in bone density resulting in an increased risk of fracture. Overactivity of osteoclasts, cells responsible for the breakdown of bone matrix, is a defining factor of osteoporosis. Previous studies found lipopolysaccharide (LPS), an inflammatory stimulus associated with bacterial infections, produces larger osteoclast in female derived precursor cells than in male derived cells. Cells that display a higher expression of the Toll-Like Receptor (TLR) signaling pathway are positively correlated to the larger osteoclasts in the female-derived committed osteoclast precursors.
The purpose of this study is to investigate sexually-divergent responses to three inflammatory signals (LPS, zymosan, and double-stranded RNA) in naïve and committed osteoclast precursors with respect to osteoclast differentiation, induction of osteoclast and inflammatory genes, and production of the inflammatory cytokine TNF.
Primary cell cultures of macrophages are harvested from mouse femurs and tibia. Macrophages are pre-exposed to receptor activator of nuclear factor kappa-Β ligand (RANKL) followed by three concentrations of LPS, zymosan and polyinosinic:polycytidylic acid (PolyI:C). Morphological assays are done using fluorescent microscopy. Genetic analysis is done using real-time quantitative polymerase chain reaction (RT-qPCR), and immune responses using enzyme linked immunoassay (ELISA). Preliminary results suggest that all three inflammatory signals can support the differentiation of osteoclast precursors. Future work will quantify and compare differentiation of osteoclasts under these conditions and ascertain whether female and male-derived cells exhibit altered sensitivity to these signals. Completion of this study may enhance mechanistic understanding of sex as a risk variable for bone loss.
