The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets.
alcoholic liver cirrhosis
bone marrow adipose tissue
connexin 43
osteocytes
sclerostin
Journal
Journal of anatomy
ISSN: 1469-7580
Titre abrégé: J Anat
Pays: England
ID NLM: 0137162
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
20
12
2021
received:
04
11
2021
accepted:
20
12
2021
pmc-release:
01
06
2024
pubmed:
4
1
2022
medline:
24
5
2022
entrez:
3
1
2022
Statut:
ppublish
Résumé
Previous studies suggested that osteocyte lacunar network disruption could play a role in the complex pathophysiology of bone changes in aging and disease. Considering that particular research interest is lacking, we aimed to assess alcoholic liver cirrhosis (ALC)-induced changes in osteocyte lacunar network and bone marrow adiposity. Immunohistochemistry was conducted to assess changes in the micro-morphology of osteocyte lacunar network and bone marrow adiposity, and expression of connexin 43 and sclerostin in vertebral and femoral samples collected from 40 cadaveric men (age range between 44 and 70 years) divided into ALC group (n = 20) and control group (n = 20). Furthermore, the assessment of the potential association between bone changes and the severity of the hepatic disorder (given by Knodell's pathohistologic scoring) was conducted. Our data revealed fewer connexin 43-positive osteocytes per vertebral and femoral bone area (p < 0.01), suggesting defective signal transduction among osteocytes in ALC individuals. Moreover, we found an ALC-induced increase in the number of adipocytes in the vertebral bone marrow (p = 0.038). Considering significant associations between the severity of liver tissue disturbances and impaired functionality of osteocyte lacunar network (Pearson's correlation analyses, p < 0.05), we may assume that timely treatment of the liver disease may delay bone impairment. ALC induced an increase in osteocytic sclerostin expression (p < 0.001), suggesting its role in mediating low bone formation among ALC individuals. Hence, medicaments targeting low bone formation may be beneficial to attenuate the bone changes among ALC patients. However, future clinical studies are required to verify the therapeutic utility of these findings.
Identifiants
pubmed: 34978341
doi: 10.1111/joa.13621
pmc: PMC9119608
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Connexin 43
0
GJA1 protein, human
0
SOST protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1162-1173Subventions
Organisme : Science Fund of the Republic of Serbia
ID : 6064549
Organisme : Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja
ID : 45005
Organisme : Alexander von Humboldt-Stiftung
ID : 3.4-1162414-SRB-IP
Informations de copyright
© 2022 Anatomical Society.
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