3BP2 deficient mice are osteoporotic with impaired osteoblast and osteoclast functions

Levaot, Noam; Simoncic, Paul D.; Dimitriou, Ioannis D.; Scotter, Andy; Rose, José La; Willett, Thomas L.; Ng, Amy; Wang, C.J.; Janmohamed, Salima; Grynpas, Marc D.; Reichenberger, Ernst; Rottapel, Robert

doi:10.1016/j.bone.2011.03.080

Cited by 20 publications

(53 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collagenous fibers are matrix proteins that constitute the bone structure and maintain the bone mechanical strength (25). Thus, bone formation is equivalent to bone mineralization, and refers to the process through which amorphous calcium phosphate and its bone mineral are deposited in bone organic matter intervals regularly (26). Ossein, referring to the collagen content of bones, is the core of bone mineralization.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

2017

View full text Add to dashboard Cite

Abstract. The aim of the present study was to determine the protective effects of resveratrol on a rat model of osteoporosis and examine the associated mechanisms of its action. Rats were randomized into the following groups: Control, osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels. Western blotting was performed to assess the protein expression of sirtuin 1 (SIRT1), nuclear factor (NF)-κB and NF-κB inhibitor (IkB) α. In the present study, the results indicated that resveratrol markedly improved the bone mineral density value, femoral porosity and bone mechanical tests in osteoporosis rats. Administration of resveratrol significantly decreased the serum levels of ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol significantly promoted the protein expression of SIRT1, suppressed NF-κB and activated the IkBα protein expression in rats with osteoporosis. In conclusion, treatment with resveratrol significantly improved the final body weight of the osteoporosis rats via the SIRT1-NF-κB signaling pathway. The present study suggested that resveratrol exerted a protective effect on osteoporosis through activation of the SIRT1-NF-κB signaling pathway in rats.

show abstract

Section: Discussionmentioning

confidence: 99%

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

2017

View full text Add to dashboard Cite

show abstract

“…Malfunction of the SH3 domain has a significant impact on such important processes as p53-mediated apoptosis and DNA repair (Jiang et al 2001), adhesion-dependent regulation by tyrosine phosphorylation (Moore and Winder 2010), stimulation of mesenchymal stem cell migration, which is important for hypoxic solid tumor development (ProulxBonneau et al 2011), osteoblast maturation and consequently bone formation (Levaot et al 2011), the assembly of amyloid fibrils and determination of their morphology (Morel et al 2010), processes associated with a number of neurodegenerative diseases, such as Alzeimer's (Morel et al 2010), tyrosine phosphatase signaling that affects SH3 binding in patients with rheumatoid arthritis (Bilwes et al 1999), bacteria adhering to host cells (Queval et al 2011) and contraction-induced injuries (Banks et al 2010). Mutations in the SH3 domain of unconventional myosin VIIa have recently been shown to cause deafness in humans, with one mutation, A1628S, located directly in its SH3 domain (Wu et al 2011).…”

Section: Regulationmentioning

confidence: 99%

SH3 domains: modules of protein–protein interactions

2012

View full text Add to dashboard Cite

Src homology 3 (SH3) domains are involved in the regulation of important cellular pathways, such as cell proliferation, migration and cytoskeletal modifications. Recognition of polyproline and a number of noncanonical sequences by SH3 domains has been extensively studied by crystallography, nuclear magnetic resonance and other methods. High-affinity peptides that bind SH3 domains are used in drug development as candidates for anticancer treatment. This review summarizes the latest achievements in deciphering structural determinants of SH3 function.

show abstract

“…3BP2 is composed of an N-terminal pleckstrin homology domain followed by a proline-rich region, and a C-terminal Src homology 2 domain. We have previously reported that 3BP2 is required for optimal B cell activation (35) and osteoclast and osteoblast function (36). In this study, we report that in the absence of 3BP2, neutrophils fail to polarize their actin cytoskeleton and migrate toward an fMLF gradient in vitro and fail to crawl to optimal sites of emigration in response to fMLF superfusion in vivo.…”

mentioning

confidence: 61%

The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation

Chen

Dimitriou

Milne

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

3BP2 is a pleckstrin homology and Src homology 2 domain-containing adapter protein mutated in cherubism, a rare autosomal-dominant human bone disorder. Previously, we have demonstrated a functional role for 3BP2 in peripheral B cell development and in peritoneal B1 and splenic marginal zone B cell-mediated Ab responses. In this study, we show that 3BP2 is required for G protein-coupled receptor-mediated neutrophil functions. Neutrophils derived from 3BP2-deficient (Sh3bp2−/−) mice failed to polarize their actin cytoskeleton or migrate in response to a gradient of chemotactic peptide, fMLF. Sh3bp2−/− neutrophils failed to adhere, crawl, and emigrate out of the vasculature in response to fMLF superfusion. 3BP2 is required for optimal activation of Src family kinases, small GTPase Rac2, neutrophil superoxide anion production, and for Listeria monocytogenes bacterial clearance in vivo. The functional defects observed in Sh3bp2−/− neutrophils may partially be explained by the failure to fully activate Vav1 guanine nucleotide exchange factor and properly localize P-Rex1 guanine nucleotide exchange factor at the leading edge of migrating cells. Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function.

show abstract

3BP2 deficient mice are osteoporotic with impaired osteoblast and osteoclast functions

Cited by 20 publications

References 0 publications

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

SH3 domains: modules of protein–protein interactions

The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation

Contact Info

Product

Resources

About