BoneKEy Reports | BoneKEy Watch
The impact of inhibiting apoptosis in osteoblasts and osteocytes
DOI:10.1038/bonekey.2013.206
Bak and Bax, genes that are required for apoptosis, were selectively deleted in osteoblasts or osteocytes and the impact on bone was assessed over a full mouse lifespan.
Deletion in osteoblasts led to an increase in bone mineral density at the femur in female mice at 6 months and 13 months of age. When the deletion was performed in osteocytes, micro-CT images showed that mice with the Bak/Bax deletion had greater numbers of intracortical pores at>20 months compared to age-matched controls. This increase in porosity was due to an increase in intracortical bone remodeling and was associated with enhanced production of vascular endothelial growth factor and RANKL.
More of the cortical osteocytes in aged mice with increased cortical porosity had abnormal features, including pyknotic nuclei with no nucleoli and a condensed cytoplasm. These dysmorphic osteocytes were concentrated around the periosteal zone.
Editor’s comment: An increased number of empty and/or micropetrotic osteocytic lacunae has been described in aging bone, and viewed as one of the mechanisms for bone fragility and the lesser response of old bones to mechanical stimulation. This elegant study used mouse models in which the molecular mechanisms of apoptosis had been deleted, resulting in long-lived osteocytes. Surprisingly, this led to further alterations of cortical bone, namely increased porosity. So the programmed death of osteocytes might be a good thing after all.
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