Osteocytes' expression of the PTH/PTHrP receptor has differing effects on endocortical and periosteal bone formation during adenine-induced CKD

摘要

Osteocytes play a key role in the pathophysiology of chronic kidney disease (CKD). However, the extent to which osteocytes contribute to abnormalities in bone turnover due to excessive levels of parathyroid hormone (PTH) remains poorly understood. The purpose of this study was to determine the extent to which bone formation and tissue strength during the progression of CKD is modified through osteocytes' response to PTH. Conditional knockout mice targeting osteocytes' expression of the PTH/PTH-related protein type 1 receptor (PPR) were subjected to adenine-induced CKD. After 6-weeks of treatment, adenine-induced CKD was found to reduce bone formation at the periosteal and endocortical surfaces of the tibia. The loss in bone mass corresponded with a significant decrease in structural-level mechanical properties. In knockout mice, the loss of PPR expression in osteocytes further exacerbated the loss in bone formation at the endocortical surface, but inhibited bone loss at the periosteal surface. In general, the effects of adenine-induced CKD were not as extensive in female mice. Collectively, these findings demonstrate that osteocytes' response to PTH under adenine-induced CKD has a unique impact on bone turnover that is specific to the periosteal and endocortical surfaces.