Fracture healing in a mouse model of Hajdu-Cheney-Syndrome with high turnover osteopenia results in decreased biomechanical stability.
Sci Rep
; 13(1): 11418, 2023 07 14.
Article
em En
| MEDLINE
| ID: mdl-37452111
ABSTRACT
Notch signaling regulates cell fate in multiple tissues including the skeleton. Hajdu-Cheney-Syndrome (HCS), caused by gain-of-function mutations in the Notch2 gene, is a rare inherited disease featuring early-onset osteoporosis and increased risk for fractures and non-union. As the impact of Notch2 overactivation on fracture healing is unknown, we studied bone regeneration in mice harboring a human HCS mutation. HCS mice, displaying high turnover osteopenia in the non-fractured skeleton, exhibited only minor morphologic alterations in the progression of bone regeneration, evidenced by static radiological and histological outcome measurements. Histomorphometry showed increased osteoclast parameters in the callus of HCS mice, which was accompanied by an increased expression of osteoclast and osteoblast markers. These observations were accompanied by inferior biomechanical stability of healed femora in HCS mice. Together, our data demonstrate that structural indices of bone regeneration are normal in HCS mice, which, however, exhibit signs of increased callus turnover and display impaired biomechanical stability of healed fractures.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoporose
/
Doenças Ósseas Metabólicas
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Síndrome de Hajdu-Cheney
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article