Fracture healing in a mouse model of Hajdu–Cheney-Syndrome with high turnover osteopenia results in decreased biomechanical stability
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Fracture healing in a mouse model of Hajdu–Cheney-Syndrome with high turnover osteopenia results in decreased biomechanical stability. / Ballhause, Tobias Malte; Jiang, Shan; Xie, Weixin; Sevecke, Jan; Dowling, Christine; Dust, Tobias; Brandt, Sabine; Mertens, Peter R; Yorgan, Timur Alexander; Schinke, Thorsten; Frosch, Karl-Heinz; Baranowsky, Anke; Keller, Johannes.
in: SCI REP-UK, Jahrgang 13, Nr. 1, 11418, 14.07.2023, S. 11418.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Fracture healing in a mouse model of Hajdu–Cheney-Syndrome with high turnover osteopenia results in decreased biomechanical stability
AU - Ballhause, Tobias Malte
AU - Jiang, Shan
AU - Xie, Weixin
AU - Sevecke, Jan
AU - Dowling, Christine
AU - Dust, Tobias
AU - Brandt, Sabine
AU - Mertens, Peter R
AU - Yorgan, Timur Alexander
AU - Schinke, Thorsten
AU - Frosch, Karl-Heinz
AU - Baranowsky, Anke
AU - Keller, Johannes
PY - 2023/7/14
Y1 - 2023/7/14
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-38638-0
DO - 10.1038/s41598-023-38638-0
M3 - SCORING: Journal article
C2 - 37452111
VL - 13
SP - 11418
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
M1 - 11418
ER -
