All the might of the osteocyte: emerging roles in chronic kidney disease

Albrecht, Lauren V.; Pereira, Renata C.; Salusky, Isidro B.

doi:10.1016/j.kint.2023.08.009

Cited by 4 publications

(1 citation statement)

References 58 publications

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“…Fibroblast growth factor 23 (FGF-23), dentin matrix protein 1 (DMP1), and sclerostin are osteocyte-secreted proteins that become elevated during the early stages of CKD when the circulating concentrations of calcium, phosphate (P), PTH, and active vitamin D are still within the normal range [7,8]. Given this, circulating osteocytic protein levels may offer a non-invasive, diagnostic biomarker of bone disease in CKD [9]. Elucidating the interactions between bone signaling and kidney function that shed light on the mechanistic underpinnings of disease will be required to facilitate the development of targeted therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy

Laster,

Pereira,

Noche

et al. 2023

Nutrients

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The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, β-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated β-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated “active” β-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

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Section: Introductionmentioning

confidence: 99%