BoneKEy Reports | BoneKEy Watch
NHERF1 and its impact on osteoblast differentiation and matrix production
Patients with mutations in Na+/H+-exchange regulatory factor-1 (NHERF1), a PDZ-domain protein that associates with Na+/H+ exchangers, the receptor for parathyroid hormone and the Npt2a Na+-phosphate cotransporter in the kidney, develop osteomalacia. NHERF1-null mice also show obvious renal phosphate wasting and skeletal abnormalities.
In this study, Liu et al. characterized NHERF1 mice to determine the role of this protein, particularly on bone formation. They first showed that NHERF1 is expressed by mineralizing osteoblasts in wild-type mice. Then, comparing NHERF1-null mice with wild-type mice, they revealed that although there were minor differences in bone volume and bone mineral density between the two types of mice, the most significant differences were in dynamic bone turnover.
NHERF1-null mice showed highly abnormal mineral deposition, consistent with dysfunctional osteoblast bone synthesis, which was evident even with dietary supplementation to prevent phosphate wasting. The authors conclude that NHERF1-null mice showed decreased bone strength because they are unable to produce bone matrix of sufficient quality.
Editor’s comment: This careful analysis of NHERF1-deficient mice specifies the crucial role of this molecule in the processes involved in bone mineralization. NHERF1 is required for renal phosphate preservation and is also crucial for normal differentiation of osteoblasts and for synthesis of the bone matrix.
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