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Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris.
Biomedicines
January 2025
Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan.
Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model.
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- Hutchison-Gilford progeria syndrome (HGPS) is a genetic disorder caused by a mutation in the LMNA gene, leading to rapid aging and serious health issues, including bone density loss and a shorter life span.
- In studies using Lmna progeria mice, researchers analyzed bone mineralization and found similarities in mineral content across various ages but noted a higher number of empty osteocyte lacunae, indicating bone deterioration.
- The findings highlighted significant reductions in bone volume and abnormal growth plates in Lmna mice, suggesting that bone dysplasia occurs due to problems in bone formation despite normal turnover rates.
3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: From monoclonal gammopathy to newly diagnosed multiple myeloma.
Bone
December 2024
Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, 14476 Potsdam, Germany; Group of Bioengineering in Regeneration and Cancer, Biogipuzkoa Health Research Institute, 20014 San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain. Electronic address:
Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites.
View Article and Find Full Text PDFMitigating aging and doxorubicin induced bone loss in mature mice via mechanobiology based treatments.
Bone
November 2024
Department of Mechanical Engineering, University of Delaware, Newark, DE, USA; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA. Electronic address:
Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy.
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