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Targeting thymidine phosphorylase as a potential therapy for bone loss associated periprosthetic osteolysis

ABSTRACT: The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. TYMP was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171542 | GEO | 2021/06/10

REPOSITORIES: GEO

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Injectable natural polymer hybrid hydrogel targeting aseptic loosening due to wear particle induced osteolysis

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Targeting thymidine phosphorylase as a potential therapy for bone loss associated periprosthetic osteolysis

Project description:Targeting thymidine phosphorylase as a potential therapy for bone loss associated periprosthetic osteolysis

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M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone

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2014-06-02 | E-GEOD-58146 | biostudies-arrayexpress

Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.

Project description: Not available

| S-EPMC8459589 | biostudies-literature

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M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone

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Lineage-committed osteoclast precursors circulate in blood and settle down into bone

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2012-01-07 | E-GEOD-26499 | biostudies-arrayexpress

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