Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy
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....
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| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/19/4127 |
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| author | Marciana Laster Renata C. Pereira Kathleen Noche Barbara Gales Isidro B. Salusky Lauren V. Albrecht |
| author_facet | Marciana Laster Renata C. Pereira Kathleen Noche Barbara Gales Isidro B. Salusky Lauren V. Albrecht |
| author_sort | Marciana Laster |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:38:22Z |
| format | Article |
| id | doaj.art-0e0a02f5b0eb4a37953118758611aa11 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T21:38:22Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-0e0a02f5b0eb4a37953118758611aa112023-11-19T14:50:34ZengMDPI AGNutrients2072-66432023-09-011519412710.3390/nu15194127Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal OsteodystrophyMarciana Laster0Renata C. Pereira1Kathleen Noche2Barbara Gales3Isidro B. Salusky4Lauren V. Albrecht5Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USADepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USADepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USADepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USADepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of California, Irvine, CA 92697, USAThe 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.https://www.mdpi.com/2072-6643/15/19/4127Wnt signalingCKD-MBDchildrensclerostinbone biopsyimmunohistochemistry |
| spellingShingle | Marciana Laster Renata C. Pereira Kathleen Noche Barbara Gales Isidro B. Salusky Lauren V. Albrecht Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy Nutrients Wnt signaling CKD-MBD children sclerostin bone biopsy immunohistochemistry |
| title | Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| title_full | Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| title_fullStr | Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| title_full_unstemmed | Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| title_short | Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| title_sort | sclerostin osteocytes and wnt signaling in pediatric renal osteodystrophy |
| topic | Wnt signaling CKD-MBD children sclerostin bone biopsy immunohistochemistry |
| url | https://www.mdpi.com/2072-6643/15/19/4127 |
| work_keys_str_mv | AT marcianalaster sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy AT renatacpereira sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy AT kathleennoche sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy AT barbaragales sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy AT isidrobsalusky sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy AT laurenvalbrecht sclerostinosteocytesandwntsignalinginpediatricrenalosteodystrophy |