ArticlePloS one2014
SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collagen-induced arthritis model.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models.Inflammation · 2025Article
- The bone phenotype associated with cherubism is independent of Caspase-1-dependent inflammasome activation in the mouse.PloS one · 2025Article
- Laggera alata Attenuates Inflammatory Response by Regulating Macrophage Polarization in Rheumatoid Arthritis Mice.Molecular biotechnology · 2024Article
- Loss-of-functionJBMR plus · 2024Article
- Tlr2/4-Mediated Hyperinflammation Promotes Cherubism-Like Jawbone Expansion in Sh3bp2 (P416R) Knockin Mice.JBMR plus · 2022Article
- SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus.International journal of molecular sciences · 2021Article
- Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis.International journal of molecular sciences · 2020Article
- Alveolar Bone Protection by Targeting the SH3BP2-SYK Axis in Osteoclasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Article
- Tankyrase (PARP5) Inhibition Induces Bone Loss through Accumulation of Its Substrate SH3BP2.Cells · 2019Review
- Osteoimmunology.Cold Spring Harbor perspectives in medicine · 2019Review
- Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis.Bone · 2018Article
- The small molecule NSM00191 specifically represses the TNF-α/NF-кB axis in foot and ankle rheumatoid arthritis.International journal of biological sciences · 2018Article
- Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveSH3BP2 is a signaling adapter protein which regulates immune and skeletal systems. Gain-of-function mutations in SH3BP2 cause cherubism, characterized by jawbone destruction. This study was aimed to examine the role of SH3BP2 in inflammatory bone loss using a collagen-induced arthritis (CIA) model.
methodsCIA was induced in wild-type (Sh3bp2(+/+)) and heterozygous P416R SH3BP2 cherubism mutant knock-in (Sh3bp2(KI/+)) mice, an SH3BP2 gain-of-function model. Severity of the arthritis was determined by assessing the paw swelling and histological analyses of the joints. Micro-CT analysis was used to determine the levels of bone loss. Inflammation and osteoclastogenesis in the joints were evaluated by quantitating the gene expression of inflammatory cytokines and osteoclast markers. Furthermore, involvement of the T- and B-cell responses was determined by draining lymph node cell culture and measurement of the serum anti-mouse type II collagen antibody levels, respectively. Finally, roles of the SH3BP2 mutation in macrophage activation and osteoclastogenesis were determined by evaluating the TNF-α production levels and osteoclast formation in bone marrow-derived M-CSF-dependent macrophage (BMM) cultures.
resultsSh3bp2(KI/+) mice exhibited more severe inflammation and bone loss, accompanying an increased number of osteoclasts. The mRNA levels for TNF-α and osteoclast marker genes were higher in the joints of Sh3bp2(KI/+) mice. Lymph node cell culture showed that lymphocyte proliferation and IFN-γ and IL-17 production were comparable between Sh3bp2(+/+) and Sh3bp2(KI/+) cells. Serum anti-type II collagen antibody levels were comparable between Sh3bp2(+/+) and Sh3bp2(KI/+) mice. In vitro experiments showed that TNF-α production in Sh3bp2(KI/+) BMMs is elevated compared with Sh3bp2(+/+) BMMs and that RANKL-induced osteoclastogenesis is enhanced in Sh3bp2(KI/+) BMMs associated with increased NFATc1 nuclear localization.
conclusionGain-of-function of SH3BP2 augments inflammation and bone loss in the CIA model through increased macrophage activation and osteoclast formation. Therefore, modulation of the SH3BP2 expression may have therapeutic potential for the treatment of rheumatoid arthritis.
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