The atherogenic<i>Scarb1</i>null mouse model shows a high bone mass phenotype

Martineau, Claude; Martin-Falstrault, Louise; Brissette, Louise; Moreau, Robert A.

doi:10.1152/ajpendo.00421.2013

Cited by 23 publications

(88 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, we observed a high femoral bone mass phenotype associated with enhanced bone formation in both male and female Scarb1-null mice (Martineau et al 2014). However, the cortical bone volume of Scarb1-null female mice was increased compared with WT mice, whereas no difference was noted for males (Martineau et al 2014).…”

Section: Resultsmentioning

confidence: 72%

“…However, the cortical bone volume of Scarb1-null female mice was increased compared with WT mice, whereas no difference was noted for males (Martineau et al 2014). Therefore, we further investigated genderspecific bone phenotype and endocrine dysfunction in Scarb1-null mice.…”

Section: Resultsmentioning

confidence: 93%

“…Two-and four-month-old mice from F7-F10 generations were used throughout the study. The mice used for the ACTH/glucocorticoid (GC) study were the same as the ones used by Martineau et al (2014); animals were added to complete the leptin study and lumbar vertebrae analyses. All experiments were performed according to UQÀ M Institutional Animal Care Committee guidelines (#611).…”

Section: Animalsmentioning

confidence: 99%

“…Scarb1-null mice show high HDL-associated cholesterol (HDL-C) levels due to impaired selective uptake of cholesterol by the liver (Rigotti et al 1997). Also, Scarb1-null male mice exhibit lack of SR-BI-mediated cholesterol uptake from HDL by the adrenal glands and concurrent impaired corticosterone response to stress and high plasma levels of ACTH (Hoekstra et al 2008, 2013, Martineau et al 2014. Given that we reported the expression of SR-BI by osteoblasts (Brodeur et al 2008), we recently characterized bone metabolism in Scarb1-null mice (Martineau et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Also, Scarb1-null male mice exhibit lack of SR-BI-mediated cholesterol uptake from HDL by the adrenal glands and concurrent impaired corticosterone response to stress and high plasma levels of ACTH (Hoekstra et al 2008, 2013, Martineau et al 2014. Given that we reported the expression of SR-BI by osteoblasts (Brodeur et al 2008), we recently characterized bone metabolism in Scarb1-null mice (Martineau et al 2014). Higher trabecular bone mass in femora and greater proliferation rate and differentiation of bone marrow mesenchymal stromal cells (MSCs) were found in Scarb1-null mice, concurrent to enhanced bone formation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

Martineau

Martin-Falstrault

Brissette

et al. 2014

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender-and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.

show abstract

Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 93%

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

Martineau

Martin-Falstrault

Brissette

et al. 2014

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

Won

Mun

Shin

et al. 2016

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective CD97, a member of the EGF-TM7 family of adhesion GPCR, is expressed on various cell types. We report here the contradictory role of CD97 in osteoclastogenesis in both basal and response to TNF treatment. We found that RANKL induced CD97 in FACS sorted osteoclast precursor cells. To elucidate the functions of CD97 in bone and inflammation, we examined the role of CD97 on osteoclastogenesis in vitro, the skeletal phenotype of CD97-deficient mice (CD97 KO), and responses to TNFα. Methods CD97 KO mouse model and TNF challenge were used to investigate the role in bone and inflammation in vivo. The effects of CD97 in bone and inflammation were assessed using histomorphometric analysis, in vitro cultures, RT-PCR and multiplex analysis of serum. Results In vitro, RANKL induced CD97 expression in bone marrow macrophages (BMM). In vivo, trabecular bone volume in the femurs of CD97 deficient female mice was increased and was associated with a decrease in osteoclast number. CD97 KO mice have reduced potential to form osteoclast-like cells (OCL) in vitro. Further, TNFα treatment augmented osteoclast formation in calvaria of CD97 KO mice in vivo by increasing the production of RANKL and other cytokines and chemokines and by reducing OPG by calvarial cells Conclusion Our findings demonstrate that CD97 is a positive regulator of OCL differentiation, influencing bone homeostasis. However, CD97 may be essential to suppress initial osteoclastogenesis in response to acute and local inflammatory stimuli.

show abstract

A Neutralizing Antibody Targeting Oxidized Phospholipids Promotes Bone Anabolism in Chow-Fed Young Adult Mice

Palmieri

Kim

Gómez-Acevedo

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Oxidized phospholipids containing phosphocholine (OxPL) are pro‐inflammatory lipid peroxidation products that bind to scavenger receptors (SRs), such as Scarb1, and toll‐like receptors (TLRs). Excessive OxPL, as found in oxidized low‐density lipoprotein (OxLDL), overwhelm these defense mechanisms and become pathogenic in atherosclerosis, nonalcoholic steatohepatitis (NASH), and osteoporosis. We previously reported that the innate IgM natural antibody E06 binds to OxPL and neutralizes their deleterious effects; expression of the single‐chain (scFv) form of the antigen‐binding domain of E06 (E06‐scFv) as a transgene increases trabecular bone in male mice. We show herein that E06‐scFv increases trabecular and cortical bone in female and male mice by increasing bone formation and decreasing osteoblast apoptosis in vivo. Homozygous E06‐scFv mice have higher bone mass than hemizygous, showing a dose effect of the transgene. To investigate how OxPL restrain bone formation under physiologic conditions, we measured the levels of SRs and TLRs that bind OxPL. We found that osteoblastic cells primarily express Scarb1. Moreover, OxLDL‐induced apoptosis and reduced differentiation were prevented in bone marrow–derived or calvaria‐derived osteoblasts from Scarb1 knockout mice. Because Scarb1‐deficient mice are reported to have high bone mass, our results suggest that E06 may promote bone anabolism in healthy young mice, at least in part, by neutralizing OxPL, which in turn promote Scarb1‐mediated apoptosis of osteoblasts or osteoblast precursors. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

show abstract

The atherogenicScarb1null mouse model shows a high bone mass phenotype

Cited by 23 publications

References 60 publications

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo

A Neutralizing Antibody Targeting Oxidized Phospholipids Promotes Bone Anabolism in Chow-Fed Young Adult Mice

Contact Info

Product

Resources

About