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

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

doi:10.1530/joe-14-0147

Cited by 15 publications

(12 citation statements)

References 63 publications

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“…We also found that there was a sex‐specific response to the loss of CD97 in terms of the bone phenotype. This was not surprising, as we and others have previously observed, in several gene‐inactivated KO models , that those animals exhibited a sex‐specific bone phenotype at the same age as examined herein. Female mice were found to exhibit alterations in the trabecular bone, while male mice showed cortical changes.…”

Section: Discussionsupporting

confidence: 88%

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

Won

Mun

Shin

et al. 2016

Arthritis & Rheumatology

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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.

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Section: Discussionsupporting

confidence: 88%

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

Won

Mun

Shin

et al. 2016

Arthritis & Rheumatology

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“…( 7 ) HDL‐dependent regulation of caveolin gene expression in osteoblasts has also been proposed as an alternative explanation of the bone phenotype. ( 7 ) Martineau and colleagues, ( 33 ) on the other hand, have proposed that Scarb1 is not required for the suppression of bone marrow stromal cell number by OxLDL. However, in that study the investigators used much higher doses of a different OxLDL preparation than the one we used, and examined only cell number—not apoptosis or proliferation.…”

Section: Discussionmentioning

confidence: 99%

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

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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)..

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“…The role of these SRs in bone homeostasis has been studied only in mice that lack SRs globally, but the data from those studies are conflicting. Indeed, it has been reported that although mice with global deletion of CD36 have low bone mass 50 , mice with global deletion of SR-B1 maintained on a normal diet have high bone mass 27 , 51 , 52 , as well as striking architectural and histomorphometric similarities with E06-scFv transgenic mice. Be that as it may, the global nature of the deletion makes it difficult to understand the role of SR-B1 specifically in osteoblasts and does not rule out the possibility that the phenotype is due to effects of OSEs in other cell types.…”

Section: Discussionmentioning

confidence: 99%

Oxidation-specific epitopes restrain bone formation

et al. 2018

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Atherosclerosis and osteoporosis are epidemiologically linked and oxidation specific epitopes (OSEs), such as phosphocholine (PC) of oxidized phospholipids (PC-OxPL) and malondialdehyde (MDA), are pathogenic in both. The proatherogenic effects of OSEs are opposed by innate immune antibodies. Here we show that high-fat diet (HFD)-induced bone loss is attenuated in mice expressing a single chain variable region fragment of the IgM E06 (E06-scFv) that neutralizes PC-OxPL, by increasing osteoblast number and stimulating bone formation. Similarly, HFD-induced bone loss is attenuated in mice expressing IK17-scFv, which neutralizes MDA. Notably, E06-scFv also increases bone mass in mice fed a normal diet. Moreover, the levels of anti-PC IgM decrease in aged mice. We conclude that OSEs, whether produced chronically or increased by HFD, restrain bone formation, and that diminished defense against OSEs may contribute to age-related bone loss. Anti-OSEs, therefore, may represent a novel therapeutic approach against osteoporosis and atherosclerosis simultaneously.

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

Cited by 15 publications

References 63 publications

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

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

Oxidation-specific epitopes restrain bone formation

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