Bone from Healthy Individuals and Patients with CKD Expresses the Sodium-Glucose Co-transporter-2 (SGLT2)

TL;DR

This study shows that bone tissue from healthy people and those with chronic kidney disease expresses SGLT2, a transporter targeted by diabetes drugs, suggesting these drugs may directly affect bone health.

Contribution

The study provides the first evidence that SGLT2 is expressed in human bone and osteoblast-like cells, challenging prior assumptions.

Findings

SLC5A2 gene expression was detected in osteoblast-like cells and bone samples from healthy individuals and CKD patients.

SGLT2 protein was identified in osteoblast-like cells and osteocytes in bone samples from both healthy and CKD subjects.

These findings suggest SGLT2 inhibitors may have direct effects on bone tissue in patients with metabolic bone diseases.

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used in type 2 diabetes mellitus management, reducing the risk of cardiovascular and renal complications. It has been stated that bone cells do not express the SGLT2 co-transporter; however, the establishment of a direct SGLT2 expression in bone and osteoblast-like cells would provide a significant advance in our understanding of direct SGLT2i effects on bone tissue from patients with metabolic bone diseases, such as chronic kidney disease or osteoporosis. SLC5A2 gene expression was investigated in osteoblast-like and renal HK-2 cells, and in human iliac crest bone samples from healthy individuals and patients with diverse stages of CKD from total RNA by real-time PCR. Additionally, SGLT2 protein qualitative expression was evaluated by Western blot in osteoblast-like cell lysates and by immunohistochemistry in bone samples from apparently healthy individuals and patients with CKD. Statistical significance was set at p < 0.05. SLC5A2 gene expression in osteoblast-like cells is comparable to HK-2 cells. Notably, in human bone samples, SLC5A2 was detected above threshold in both healthy individuals and patients with CKD; thus, absolute quantification of its transcript number of copies was feasible in bone samples for these conditions. SGLT2 protein was detected in osteoblast-like cells. Additionally, this protein was immunodetected in osteocytes embedded in mineralized trabecular and cortical bone samples from healthy subjects and patients with CKD. SLC5A2 gene expression and SGLT2 protein were detected in human osteoblast-like cells and bone from both healthy individuals and patients with CKD. These findings constitute an essential step toward advancing the understanding of effects, if any, of SGLT2 inhibitors on bone tissue from patients with CKD.

The online version contains supplementary material available at 10.1007/s00223-026-01498-7.

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