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Transcriptome analysis of the mandibles from FcgRIIB-deficient mouse model of lupus

ABSTRACT: To identify the extensive complexity of transcriptome in Fc gamma receptor IIB knockout (FcgRIIB−/−) mandibles. We performed gene expression profiling of mandibular bone from wild-type (WT) and FcgRIIB−/− mice at 6 months of age. Our study reports the first transcriptomic analysis in mandibles of FcgRIIB-deficient mice using RNA-sequencing (RNA-seq). The data were validated by qPCR analysis. qPCR analysis revealed similar results compared to RNA-seq data. This finding disclosed the relevant differentially expressed genes (DEGs) and clarify the mechanism underlying the pathogenesis of osteopenia. We provide novel candidate genes and enriched pathways that contribute to mandibular bone loss in FcgRIIB−/− mice during lupus development. Sufu and Serpina12 were identified as candidate molecular targets regulating osteoclastogenesis and osteogenesis, respectively.

ORGANISM(S): Mus musculus

PROVIDER: GSE179155 | GEO | 2021/09/29

REPOSITORIES: GEO

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Project description:Background Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. Materials and Methods To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. Results Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclast in the subchondal bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. Conclusions Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

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