Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice.
Astrid M SchoppaXiangxu ChenJan-Moritz RamgeAnna VikmanVerena FischerMelanie Haffner-LuntzerJana RieggerJan TuckermannKarin Scharffetter-KochanekAnita IgnatiusPublished in: Disease models & mechanisms (2022)
Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors contributing to osteoporosis. Mitochondrial (mt)ROS, as the superoxide anion (O2-) generated during mitochondrial respiration, are eliminated in the young organism by antioxidant defense mechanisms, including superoxide dismutase 2 (SOD2), the expression and activity of which are decreased in aging mesenchymal progenitor cells, accompanied by increased mtROS production. Using a mouse model of osteoblast lineage cells with Sod2 deficiency, we observed significant bone loss in trabecular and cortical bones accompanied by decreased osteoblast activity, increased adipocyte accumulation in the bone marrow and augmented osteoclast activity, suggestive of altered mesenchymal progenitor cell differentiation and osteoclastogenesis. Furthermore, osteoblast senescence was increased. To date, there are only a few studies suggesting a causal association between mtROS and cellular senescence in tissue in vivo. Targeting SOD2 to improve redox homeostasis could represent a potential therapeutic strategy for maintaining bone health during aging.
Keyphrases
- bone loss
- bone mineral density
- oxidative stress
- reactive oxygen species
- bone marrow
- dna damage
- postmenopausal women
- bone regeneration
- induced apoptosis
- amyotrophic lateral sclerosis
- mouse model
- stem cells
- body composition
- poor prognosis
- cell death
- public health
- mesenchymal stem cells
- insulin resistance
- healthcare
- endothelial cells
- cell cycle arrest
- hydrogen peroxide
- type diabetes
- single cell
- adipose tissue
- fatty acid
- nitric oxide
- risk assessment
- anti inflammatory
- cell proliferation
- case control
- endoplasmic reticulum stress
- drug delivery
- health promotion
- high fat diet induced
- replacement therapy
- drug induced