Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss

Onal, Melda; Xiong, Jinhu; Chen, Xinrong; Thostenson, Jeff D.; Almeida, Maria; Manolagas, Stavros C.; O’Brien, Charles A.

doi:10.1074/jbc.m112.377945

Cited by 213 publications

(202 citation statements)

References 53 publications

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“…Consistent with this finding, deletion of ER␣ from osteocytes has no effect on osteoclast number (26,27). We and others have shown that the amount of soluble RANKL protein in bone marrow supernatants does increase with either estrogen or androgen deficiency (12,28,29). However, whether this increase in soluble RANKL contributes to the increase in bone resorption caused by these conditions is unknown.…”

Section: Discussionsupporting

confidence: 68%

“…The latter finding was unexpected given that RANKL produced by B lymphocytes themselves is also required for this phenomenon (12). The mechanisms by which osteocyte RANKL controls B cell number are unclear but appear to be indirect as deletion of the receptor for RANKL from B cells does not alter B cell number (19).…”

Section: Discussionmentioning

confidence: 80%

“…Estrogen deficiency also causes a striking increase in B lymphocyte number in the bone marrow (10,11). Moreover, deletion of the Tnfsf11 gene from B cells prevents both the increase in B cell number and the increase in cancellous osteoclast number caused by ovariectomy (12). These findings suggest that estrogen may suppress osteoclast number in part by suppressing B cell number in the bone marrow.…”

mentioning

confidence: 64%

“…Osteocyte RANKL Is Required for the Increase in B Cells after Ovariectomy-We have shown previously that deletion of RANKL from B lymphocytes prevents the increase in bone marrow B cells and cancellous osteoclasts after ovariectomy (12). This observation suggested a possible link between the two phenomena.…”

Section: Osteocyte Rankl Is Required For Ovariectomy-induced Bonementioning

confidence: 78%

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RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

Fujiwara

Piemontese

Liu

et al. 2016

Journal of Biological Chemistry

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Edited by Luke O'NeillThe cytokine receptor activator of NFB ligand (RANKL) produced by osteocytes is essential for osteoclast formation in cancellous bone under physiological conditions, and RANKL production by B lymphocytes is required for the bone loss caused by estrogen deficiency. Here, we examined whether RANKL produced by osteocytes is also required for the bone loss caused by estrogen deficiency. Mice lacking RANKL in osteocytes were protected from the increase in osteoclast number and the bone loss caused by ovariectomy. Moreover, these mice did not exhibit the increase in bone marrow B lymphocytes caused by ovariectomy that occurred in control littermates. Deletion of estrogen receptor ␣ from B cells did not alter B cell number or bone mass and did not alter the response to ovariectomy. In addition, lineage-tracing studies demonstrated that B cells do not act as osteoclast progenitors in estrogen-replete or estrogen-deficient mice. Taken together, these results demonstrate that RANKL expressed by osteocytes is required for the bone loss as well as the increase in B cell number caused by estrogen deficiency. Moreover, they suggest that estrogen control of B cell number is indirect via osteocytes and that the increase in bone marrow B cells may be a necessary component of the cascade of events that lead to cancellous bone loss during estrogen deficiency. However, the role of B cells is not to act as osteoclast progenitors but may be to act as osteoclast support cells.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 64%

Section: Osteocyte Rankl Is Required For Ovariectomy-induced Bonementioning

confidence: 78%

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RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

Fujiwara

Piemontese

Liu

et al. 2016

Journal of Biological Chemistry

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“…48 The number of RANKL-expressing B lymphocytes in the bone marrow increases after OVX. 49 Recently, Onal et al 50 demonstrated that RANKL produced by B cells and not by T cells have a role in OVX-induced bone loss in mice. This paper disagrees with previous reports showing a fundamental role of RANKL produced by T cells in OVX-induced bone loss.…”

Section: Inflammatory Diseases Immune System and Bonementioning

confidence: 99%

Osteoimmunology: from mice to humans

Sassi¹

2016

Bonekey Reports

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The immune system has been recognized as one of the most important regulators of bone turnover and its deregulation is implicated in several bone diseases such as postmenopausal osteoporosis and inflammatory bone loss; recently it has been suggested that the gut microbiota may influence bone turnover by modulation of the immune system. The study of the relationship between the immune system and bone metabolism is generally indicated under the term 'osteoimmunology'. The vast majority of these studies have been performed in animal models; however, several data have been confirmed in humans as well: this review summarizes recent data on the relationship between the immune system and bone with particular regard to the data confirmed in humans.

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Immunobiology and Bone

Pacifici

Weitzmann

2018

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss

Cited by 213 publications

References 53 publications

RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

RANKL (Receptor Activator of NFκB Ligand) Produced by Osteocytes Is Required for the Increase in B Cells and Bone Loss Caused by Estrogen Deficiency in Mice

Osteoimmunology: from mice to humans

Immunobiology and Bone

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