Journal article
Glutathione Peroxidase 4 Overexpression Alters Bone Remodeling in response to Injury and Overloading
Free radical biology & medicine, Vol.224(Supplement 1), pp.S8-S9
11/01/2024
DOI: 10.1016/j.freeradbiomed.2024.10.010
Abstract
Osteoporosis afflicts over 10 million Americans over the age of 50, decreasing their quality of life. Bone remodeling maintains bone health and enables adaptation to changes in mechanical load. These changes activate bone absorbing cells, osteoclasts, and bone secreting cells, osteoblasts, to effect remodeling. Either case has been shown to involve peroxisome proliferator-activated receptor gamma (PPAR-γ). Because PPAR-γ is activated by lipid peroxidation products, we hypothesized that overexpression of lipid antioxidant glutathione peroxidase 4 (GPx4) would alter bone remodeling and PPAR-γ expression during physiologically relevant mechanical overloads.
To test this, mice aged either 12-weeks or 18-months underwent a medial meniscal destabilization (MMD) to induce mechanical overload. This leads to arthritis and compensatory overloading of the opposite limb by 12-weeks. Mice were assessed at 24 h and 12-weeks after MMD for indications of bone remodeling including bone volume of the tibial metaphysis and immunohistochemical staining of PPAR-γ.
When evaluating bone volume 12-weeks after MMD, we observed that WT mice had high bone volume in both the contralateral and injured limbs whereas TgGPx4 had decreased bone volume in their contralateral limb. There were no differences in the corresponding, uninjured limbs of young or old mice 24 h after MMD. This suggests aberrant responses to mechanical overload in the bone of TgGPx4 mice over time. To further examine the bone of old mice, we evaluated PPAR-γ expression in 18-month-old mice 24 h after MMD, PPAR-γ expression trended higher in the injured limb of WT, but old TgGPx4 mice had decreased PPAR-γ expression with injury. This supports the hypothesis that overexpression of GPx4 may disrupt PPAR-γ activity, but further study is needed to determine cell-type specific involvement of PPAR-γ in this complex physiological response. We conclude that lipid peroxidation is a necessary process for bone remodeling induced by mechanical overload.
Details
- Title: Subtitle
- Glutathione Peroxidase 4 Overexpression Alters Bone Remodeling in response to Injury and Overloading
- Creators
- Madeline Hines - University of IowaSuryamin Liman - University of IowaDouglas Fredericks - University of Iowa, Orthopedics and RehabilitationHolly Van Remmen - Oklahoma Medical Research FoundationMitchell Coleman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.224(Supplement 1), pp.S8-S9
- DOI
- 10.1016/j.freeradbiomed.2024.10.010
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/01/2024
- Academic Unit
- Orthopedics and Rehabilitation; Radiation Oncology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984748156702771
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