Relationship between serum RANKL and RANKL in bone

Findlay, David M.; Atkins, Gerald J.

doi:10.1007/s00198-011-1740-9

Cited by 64 publications

(51 citation statements)

References 60 publications

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“…The latter observation for IL-6 is in accordance with the previously observed dual role of IL-6 on osteoclasts [17,22,23]. Although previous reports have shown an inverse relationship between RANKL bone mRNA and serum levels in OA males [37], our results of this correlation analysis did not reach the level of significance. The reason is most likely due to low statistical power as there were only three OA males with serum RANKL levels.…”

Section: Discussionsupporting

confidence: 88%

The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues

2012

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BackgroundPro-inflammatory cytokines possess osteoclastogenic or anti-osteoclastogenic activities. They influence osteoclasts directly or via the receptor activator of nuclear factor κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) system. Recent evidence suggests that inflammation may play a role in osteoporosis (OP) and osteoarthritis (OA). We aimed therefore to determine whether there is a difference between both groups: first, in the expression of the osteoclastogenic and anti-osteoclastogenic cytokines, second, in correlation of these cytokines with bone mineral density (BMD) and levels of bone turnover markers (BTM) and third, in correlation between the expression of these cytokines and osteoclast specific genes and RANK/RANKL/OPG genes.MethodsHuman bone samples from 54 age and sex matched patients with OP or OA were collected during hip arthroplasty surgery. The expression of 25 genes encoding pro-inflammatory cytokines, their receptors, osteoclast specific genes and RANK/RANKL/OPG genes was measured using quantitative real-time PCR. Total hip, femoral neck and lumbar spine BMD and BTM in blood samples were measured. The comparison between OP and OA was assessed using Student's t-test or Mann-Whitney U test and correlations between gene expression, BMD and BTM were determined using nonparametric correlation.ResultsThe results demonstrated a higher expression of interleukin (IL)-6 and IL-1α in OP, and interferon (IFN)-γ in OA (p < 0.0005). Negative correlations of total hip BMD with tumor necrosis factor-α (TNF-α) in OA and with RANKL/RANK in OP were found (p < 0.05). Significant correlations with BTM were shown for IL-1α and IFN-γ in OP (rho = 0.608 and -0.634) and for TNF-α, IL-6 and transforming growth factor-β1 (TGF-β1) in OA (rho = 0.591, -0.521 and 0.636). Results showed OP specific negative correlations (IFN-γ with ITGB3, IFN-β1 with CTSK, tartrate resistant acid phosphatase (TRAP), CALCR, RANK, RANKL, IL-1α with CTSK, OPG, IL-17A with CALCR) and positive (TGF-β1 with CTSK, TRAP, RANK), and OA specific negative (IL-1α with osteoclast associated immunoglobulin-like receptor (OSCAR), TNF-α with RANK, RANKL, OPG) and positive (IL-6 with RANK, RANKL, OPG) correlations.ConclusionsOur results demonstrate that the relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human OP and OA bone and could present an important factor for characteristics of OP and OA bone phenotypes.

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Section: Discussionsupporting

confidence: 88%

The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues

2012

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“…Most commercial kits measure free RANKL, which is w1/1000 of the total serum RANKL. This feature explains that some investigators have reported undetectable levels of RANKL in up to 50% of individuals (43). Moreover, the antibodies may measure different RANKL types of the soluble molecular species of the cytokine (44), a conceivable difficulty given the research profile of the available assays.…”

Section: Other Regulatorsmentioning

confidence: 99%

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Sanz-Salvador

Garcı́a-Pérez

Tarı́n

et al. 2015

European Journal of Endocrinology

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Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use.

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“…These disorders might be imposed predominantly by the changes occurring directly in tumor tissue, but we cannot ignore the fact that serum levels of RANK/RANKL/OPG components, as well as the level of any other serological marker, cannot be completely determined by the secretion of corresponding protein from tumor cells. It depends on various physiological factors, on probable production of proteins studied by other tissues, and on the presence of concomitant diseases, in particular, osteoporosis and inflammatory processes [14,15].…”

Section: Discussionmentioning

confidence: 99%

Receptor Activator of Nuclear Transcription Factor Nf-b (Rank), Its Ligand (Rankl) and Natural Inhibitor Osteoprotegerin (Opg) in Blood Serum of Primary Bone Tumor Patients: Association With Clinicopathological Features and Inflammatory Cytokines Levels

Kushlinskii¹,

Es²,

Timofeev³

et al. 2017

RAD Conference Proceedings

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Abstract. RANK/RANKL/OPG system (the key regulator of bone homeostasis) component levels were measured in blood serum of 199 patients with primary bone tumors and tumor-like lesions: 121 with bone sarcomas (53 osteosarcoma, 46 chondrosarcoma, 12 chordoma, 8 Ewing sarcoma), 32 with borderline giant cell bone tumor (GCBT), 46 with benign bone neoplasms; 131 persons comprised the control group. OPG, sRANKL, sRANK, IL-6, 8, 16 serum levels were measured by standard ELISA kits. Giant-cell bone tumor (GCBT) manifesting high osteoclastogenic and osteolytic activities was characterized by high serum content of all three components studied and the highest sRANKL/OPG ratio. The group of patients with various benign bone tumors and tumor-like lesions displayed similar to GCBT, but lower indices. Malignant bone tumor patients could be divided into 2 subgroups with opposite characteristics: osteosarcoma and Ewing sarcoma patients demonstrated low sRANK and high sRANKL levels, while chondrosarcoma and chordoma patients, on the contrary -high sRANK and low sRANKL levels. The highest IL-6 levels were revealed in GCBT patients, while serum IL-8 and IL-16 did not differ between groups. Thus, disturbances in osteolysis activators and inhibitors balance in blood serum of primary bone tumor patients were revealed. Their extent depended on neoplasm character (malignant, borderline, or benign) and histological structure of malignant sarcomas. Most prominent changes were found in GCBT characterized by active bone destruction and an accepted target of anti-RANKL antibody denosumab treatment. Hence, the proteins studied can be regarded as promising serologic markers and therapeutic targets in this rare disease.

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Relationship between serum RANKL and RANKL in bone

Cited by 64 publications

References 60 publications

The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues

The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Receptor Activator of Nuclear Transcription Factor Nf-b (Rank), Its Ligand (Rankl) and Natural Inhibitor Osteoprotegerin (Opg) in Blood Serum of Primary Bone Tumor Patients: Association With Clinicopathological Features and Inflammatory Cytokines Levels

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