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. 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nutrients - 15(2023), 19 vom: 25. Sept. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Laster, Marciana [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Beta Catenin |
|---|
| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 10.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/nu15194127 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363293728 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363293728 | ||
| 003 | DE-627 | ||
| 005 | 20240210232738.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/nu15194127 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1286.xml |
| 035 | |a (DE-627)NLM363293728 | ||
| 035 | |a (NLM)37836411 | ||
| 035 | |a (PII)4127 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Laster, Marciana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.10.2023 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CKD-MBD | |
| 650 | 4 | |a Wnt signaling | |
| 650 | 4 | |a bone biopsy | |
| 650 | 4 | |a children | |
| 650 | 4 | |a immunofluorescence | |
| 650 | 4 | |a immunohistochemistry | |
| 650 | 4 | |a sclerostin | |
| 650 | 7 | |a beta Catenin |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 700 | 1 | |a Pereira, Renata C |e verfasserin |4 aut | |
| 700 | 1 | |a Noche, Kathleen |e verfasserin |4 aut | |
| 700 | 1 | |a Gales, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Salusky, Isidro B |e verfasserin |4 aut | |
| 700 | 1 | |a Albrecht, Lauren V |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nutrients |d 2009 |g 15(2023), 19 vom: 25. Sept. |w (DE-627)NLM206140738 |x 2072-6643 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:19 |g day:25 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/nu15194127 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 19 |b 25 |c 09 | ||