Serum Levels of Receptor Activator of Nuclear Factor κB Ligand (RANKL) in Healthy Women and Men

Kerschan‐Schindl, Katharina; Wendlova, J; Kudlacek, Stefan; Gleiß, Andreas; Woloszczuk, W; Pietschmann, Péter

doi:10.1055/s-2007-993142

Cited by 26 publications

(26 citation statements)

References 23 publications

(27 reference statements)

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“…The gender differences may be due to effects of estrogen, which has been shown to inhibit RANKL signaling [28]. Gender differences in serum RANKL in our mice are also consistent with the gender differences reported in human studies, with levels almost twice as high in women as in men [27, 31]. Serum RANKL levels are also influenced by female hormonal cycling, with levels higher in the follicular vs. luteal phases [32].…”

Section: Discussionsupporting

confidence: 82%

Enhanced Mineralization Potential of Vascular Cells from SM22α-Rankl tg Mice

et al. 2012

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Vascular calcification, prevalent in diabetes and chronic kidney disease, contributes to morbidity and mortality. To investigate the effect of receptor activator of NF-kB ligand (RANKL) on vascular calcification in vivo, transgenic mice, where RANKL expression was targeted to vascular smooth muscle cells using SM22alpha promoter (SM22α-Rankltg), was created. Sixteen-month-old male SM22α-Rankltg mice had higher body weight and higher serum calcium levels but lower lumbar bone mineral density (BMD) compared with age- and gender-matched WT littermates. BMD of long bones, body fat (% of weight) of the leg, and serum levels of phosphate and RANKL were not significantly different. No significant differences in these parameters were observed in the female mice. Histological analysis did not reveal calcium deposits in the aortic roots of the SM22α-Rankltg mice. To analyze the osteoblastic differentiation and mineralization potentials of vascular cells, aortic smooth muscle cells (SMCs) were isolated and cultured. Results showed that SM22α-Rankltg SMCs had higher baseline alkaline phosphatase (ALP) activity, but not the baseline matrix calcification. When induced by the PKA agonist, forskolin, ALP activity was greater in SM22α-Rankltg than in WT SMCs. Realtime RT-qPCR revealed higher baseline expression of ALP and ankylosis genes, but lower osteoprotegerin gene, in SM22α-Rankltg SMCs. Matrix mineralization induced by inorganic phosphate or forskolin was greater in SM22α-Rankltg than in WT SMCs. Treatment of these cells with the ALP inhibitor, levamisole, abolished forskolin-induced matrix mineralization but not Pi-induced matrix mineralization. These findings suggest that RANKL overexpression in the vasculature may promote mineralization potential.

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Section: Discussionsupporting

confidence: 82%

Enhanced Mineralization Potential of Vascular Cells from SM22α-Rankl tg Mice

et al. 2012

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“…Data from our laboratory [18] show that, in aged male rats, serum RANKL levels and ex vivo osteoclast generation are diminished despite demonstrable evidence of increased bone resorption. A decline in serum RANKL levels with age has also been registered in human studies [19] and is in line with the age-related decline of RANKL expression in T cells ( fig. 3 ).…”

Section: Bone Biology and Agingsupporting

confidence: 84%

Osteoporosis: An Age-Related and Gender-Specific Disease – A Mini-Review

et al. 2008

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Osteoporosis, a classical age-related disease and known to be more common in women than in men, has been reported increasingly often in men during the past few years. Although men at all ages after puberty have larger bones than women, resulting in greater bending strength, mortality after a hip fracture, one of the major complications of osteoporosis, is more common in men than in women. Sex hormone deficiency is associated with unrestrained osteoclast activity and bone loss. Even though estrogen deficiency is more pronounced in women, it appears to be a major factor in the pathogenesis of osteoporosis in both genders. In contrast to osteoporosis in postmenopausal women, the treatment of osteoporosis in men has been scarcely reported. Nevertheless, some drugs commonly used for the treatment of osteoporosis in women also appear to be effective in men. The aim of this study is to review primary osteoporosis in the elderly with particular emphasis on gender-related aspects.

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“…For example, RANKL mRNA levels were negatively associated with BV/TV and strongly positively associated with ES/BS. In contrast, the relationship between serum total RANKL levels and bone structural and circulating parameters was in each case the inverse of that between these parameters and RANKL Healthy women and men Men higher average free RANKL than women; levels decrease by 13% each 5 years [49] Postmenopausal women OPG correlates with age; free RANKL-positive correlation with age and negative correlation with vertebral BMD [50] Paget's disease patients OPG levels increased; free RANKL similar to healthy controls [51] Rheumatoid arthritis OPG:free RANKL ratio at baseline predicted 5-and 11-year progression of joint damage [52,53] Spinal cord injury patients Reduced free RANKL and higher OPG levels than able-bodied controls [54] Nontraumatic fracture patients Low free RANKL predictor for nontraumatic fracture [37] Middle-aged Korean males Negative correlation between OPG and spine BMD; free RANKL-negative relationship with femoral neck BMD [55] Juvenile idiopathic arthritis Lower levels of OPG; RANKL increased with disease severity [56] Female juvenile idiopathic arthritis patients Higher levels of free RANKL in active disease with bone erosions compared with controls [57] Hip replacement patients Lower median free RANKL levels associated with osteolysis [58] Ankylosing spondylitis Higher OPG and sRANKL; OPG correlated positively with immobility [59] mRNA levels, even though none of these relationships achieved significance [27]. Although these intriguing results need to be confirmed in additional studies, they suggest that, at least in an elderly male cohort, serum total RANKL represents the inverse of active RANKL in bone.…”

Section: Relationship Between Serum Rankl and Rankl Mrna Levels In Bonementioning

confidence: 86%

Relationship between serum RANKL and RANKL in bone

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Atkins

2011

Osteoporos Int

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It is now well accepted that the molecule receptor activator of NFκB ligand (RANKL) and osteoprotegerin play key roles in regulating physiological and pathological bone turnover. There are a large number of published reports of circulating RANKL levels in both health and pathology. However, interpretation of these data has been elusive, and the relationship between circulating RANKL and RANKL levels in bone is still not clear. This review explores this subject, documenting the possible origins of circulating RANKL and suggesting additional information that is required before serum RANKL levels can provide useful diagnostic or research information.

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Serum Levels of Receptor Activator of Nuclear Factor κB Ligand (RANKL) in Healthy Women and Men

Abstract: This study showed that serum levels of free RANKL and total RANKL decrease with age, and also revealed some gender-related differences.

Cited by 26 publications

References 23 publications

Enhanced Mineralization Potential of Vascular Cells from SM22α-Rankl tg Mice

Enhanced Mineralization Potential of Vascular Cells from SM22α-Rankl tg Mice

Osteoporosis: An Age-Related and Gender-Specific Disease – A Mini-Review

Relationship between serum RANKL and RANKL in bone

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