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Accelerated development of instability-induced osteoarthritis in transgenic mice overexpressing SOST.

ABSTRACT: OBJECTIVE:Sclerostin (SOST), acting as a Wnt antagonist, has been shown to play a key role in regulating bone homestasis, and has also been linked to osteoarthritis (OA) development. Here, we investigated whether overexpressing SOST could affect OA development after destabilization of the medial meniscus (DMM) using SOST transgenic (Tg) mice. METHODS:Bone and cartilage phenotypes of SOST Tg mice at 10 weeks of age were investigated by dual x-ray absorptiometry (DXA) and histology. Subsequently, 10-week-old SOST Tg mice and their wild-type (WT) littermates were subjected to DMM or sham surgery. Knee joints were isolated to evaluate the cartilage damage and the subchondral bone plate thickness at 2 and 8 weeks post-surgery. The changes of chondrocyte anabolic and catabolic responses after IL-1? or TNF? stimulation, ?-catenin signaling and apoptosis were also measured. RESULTS:Ten-week-old SOST Tg mice were identical to their WT littermate males except that they displayed digit abnormalities and osteopenic, whereas more severe OA was observed in SOST Tg mice at 2 and 8 weeks post-DMM. In addition, DMM resulted in significantly greater subchondral bone changes compared with sham surgery in SOST Tg mice at 8 weeks post-surgery. The accelerated OA in SOST Tg mice may be associated with reduced ?-catenin signaling and increased chondrocyte apoptosis. CONCLUSION:Overexpressing SOST led to accelerated development of instability-induced OA. Our data further highlight that cartilage homeostasis requires finely tuned Wnt signaling.

SUBMITTER: Zhou S

PROVIDER: S-EPMC6965855 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Accelerated development of instability-induced osteoarthritis in transgenic mice overexpressing SOST.

Zhou Sheng S Ge Yuxiang Y Li Yixuan Y Bao Zhengyuan Z Yao Chen C Teng Huajian H Jiang Qing Q

International journal of clinical and experimental pathology 20171101 11

<h4>Objective</h4>Sclerostin (SOST), acting as a Wnt antagonist, has been shown to play a key role in regulating bone homestasis, and has also been linked to osteoarthritis (OA) development. Here, we investigated whether overexpressing SOST could affect OA development after destabilization of the medial meniscus (DMM) using <i>SOST transgenic (Tg)</i> mice.<h4>Methods</h4>Bone and cartilage phenotypes of <i>SOST Tg</i> mice at 10 weeks of age were investigated by dual x-ray absorptiometry (DXA) ...[more]

PMID: 31966426

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Accelerated development of instability-induced osteoarthritis in transgenic mice overexpressing SOST.

Publications

Accelerated development of instability-induced osteoarthritis in transgenic mice overexpressing SOST.

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