scholarly journals The Role of the Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Cytokine System in Primary Hyperparathyroidism

2008 ◽  
Vol 93 (3) ◽  
pp. 967-973 ◽  
Author(s):  
Inaam A. Nakchbandi ◽  
Robert Lang ◽  
Barbara Kinder ◽  
Karl L. Insogna
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Primary Hyperparathyroidism ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Mineral Density ◽  
Receptor Activator ◽  
Markers Of Bone Resorption

Abstract Context: The mechanisms of action of PTH on bone in vivo remain incompletely understood. The objective of this investigation was to examine changes in serum levels of receptor activator of nuclear factor-κB ligand and osteoprotegerin (OPG) in primary hyperparathyroidism and their relationship to bone loss. Patients and Methods: Twenty-nine patients with primary hyperparathyroidism had baseline circulating soluble receptor activator of nuclear factor-κB ligand (sRANKL) and OPG measured. The relationship to biochemical markers of bone turnover and changes in bone mineral density over 2 yr was examined. Results: Baseline sRANKL levels were elevated (1.7 ± 0.1 pmol/liter), whereas OPG remained in the normal range (5.6 ± 0.4 pmol/liter). Circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption (urine deoxypyridinoline cross-links: r = 0.51, P < 0.01; serum N-telopeptide of type I collagen: r = 0.37, P < 0.05). Furthermore, sRANKL correlated with both IL-6 and IL-6 soluble receptor (IL-6sR) (r = 0.47, P < 0.05 and r = 0.55, P < 0.005, respectively). Serum sRANKL levels also correlated with bone loss at the total femur (r = −0.53, P < 0.01). Lastly, a high value of sRANKL in combination with values of IL-6 and IL-6sR in the upper quartile (sRANKL ≥ 1.81 pg/ml, IL −6 ≥ 11.8 pg/ml, and IL-6sR ≥ 45.6 ng/ml) defined a group of four women with significantly greater rates of bone loss at the total femur than the remaining patients (−2.7 ± 1.7% vs. +0.5 ± 0.3%; n = 4 vs. n = 19, P < 0.05). Conclusion: Determination of circulating levels of sRANKL may be useful in identifying patients with mild primary hyperparathyroidism at greater risk for bone loss. The fact that circulating sRANKL did not correlate with PTH but did correlate with markers of bone resorption suggests that skeletal responsiveness to PTH may differ in this disease.

scholarly journals Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide

2008 ◽  
Vol 158 (3) ◽  
pp. 411-415 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Dimirtios G Goulis ◽  
Stergios A Polyzos ◽  
Spiridon Gerou ◽  
Vasiliki Pavlidou ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Serum Levels ◽  
Nuclear Factor Κb ◽  
Acute Effect ◽  
Type I ◽  
Nuclear Factor ◽  
Mineral Density ◽  
Serum Samples ◽  
Established Osteoporosis ◽  
Receptor Activator

ObjectiveThe mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1–34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) in women with established osteoporosis.DesignTwenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7±1.6 years) received daily injections of 20 μg TPTD for 12 months.MethodsSerum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment.ResultsSerum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P<0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels.ConclusionsTPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD.

scholarly journals Ιδιοπαθής υπερασβεστιουρία στην παιδική ηλικία

2017 ◽  
Author(s):  
Μαρία Παύλου
Keyword(s):  
Type I Collagen ◽  
Cross Linking ◽  
Type I ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Receptor Activator ◽  
Carboxy Terminal ◽  
Nuclear Factor Kb

Η ιδιοπαθής υπερασβεστιουρία (ΙΥΑ) στα παιδιά έχει επιπολασμό 2,2-17,7%. Ποσοστό 2635% των ασθενών εμφανίζει μειωμένη οστική πυκνότητα, που αποδίδεται μάλλον σε αυξημένη οστική απορρόφηση και/ή οστικό ανασχηματισμό, καθώς καταγράφεται φυσιολογική κατά μήκος αύξηση των οστών στα περισσότερα παιδιά με ΙΥΑ. Περιορισμένες είναι οι μελέτες εκτίμησης βιοχημικών δεικτών οστικού μεταβολισμού, αλλά και γονιδιακού ελέγχου σε παιδιά με ΙΥΑ στην διεθνή βιβλιογραφία και καμία στην ελληνική. Επίσης, δεν πραγματοποιήθηκαν μελέτες εκτίμησης των κυτταροκινών οστεοκλαστογένεσης οστεοπροτεγερίνη (osteoprotegerin, OPG) και sRANKL (soluble receptor activator of nuclear factor kB ligand) σε ασθενείς με ΙΥΑ. Σκοπός της μελέτης ήταν η εκτίμηση των βιοχημικών δεικτών οστικής παραγωγής, αλκαλική φωσφατάση (alkaline phosphatase, ALP) και οστεοκαλσίνη (osteocalcin, OC) και οστικής απορρόφησης β-Crosslaps (serum Carboxy-terminal cross-linking telopeptide of type I collagen) και της OPG και sRANKL στον ορό σε παιδιά με ΙΥΑ. Επίσης έγινε γονιδιακή ανάλυση των πολυμορφισμών του γονιδίου του ασβεστιοευαίσθητου υποδοχέα (Calcium sensing Receptor, CaSR). Πενήντα παιδιά με ΙΥΑ αποτέλεσαν την ομάδα ασθενών και 60 υγιή παιδιά την ομάδα ελέγχου. Οι ασθενείς εκτιμήθηκαν κατά τον χρόνο της διάγνωσης και 3 μήνες μετά την εφαρμογή διαιτητικών οδηγιών αντιμετώπισης της ΙΥΑ. Οι ασθενείς της μελέτης μας είχαν σχετικά ήπια προς μέτρια υπερασβεστιουρία (6,49±2,03 mg/Kg/day) κατά την ένταξη στην μελέτη. Μετά την εφαρμογή των διατροφικών οδηγιών, μείωσαν σημαντικά τα επίπεδα του Ca στα ούρα 24ώρου και τον λόγο του Ca προς κρεατινίνη στα δείγματα ούρων, χωρίς όμως να φτάνουν τις φυσιολογικές τιμές. Τα επίπεδα της ALP και OC και το ύψος των ασθενών δεν διέφεραν από της ομάδας ελέγχου, που δείχνει ανεπηρέαστη οστική παραγωγή στους ασθενείς. Τα επίπεδα των β-Crosslaps των ασθενών, στους δύο χρόνους εκτίμησης, ήταν υψηλότερα από των μαρτύρων, ενώ καταγράφηκε τάση μείωσης της μέσης τιμής μετά την τρίμηνη παρέμβαση. Το εύρημα δείχνει αυξημένη οστική απορρόφηση στους ασθενείς με τάση βελτίωσης κατά τον επανέλεγχο. Ο λόγος β-Crosslaps/OC στους ασθενείς κατά την ένταξη στην μελέτη ήταν αυξημένος συγκριτικά με των μαρτύρων, καταγράφοντας υψηλότερο ρυθμό οστικής απορρόφησης συγκριτικά με οστικής παραγωγής. Τα επίπεδα των OPG και sRANKL των ασθενών, στους δύο χρόνους εκτίμησης δε διέφεραν από των μαρτύρων. Ωστόσο, ο λόγος sRANKL/OPG στους ασθενείς κατά την ένταξη στην μελέτη ήταν ελαφρά χαμηλότερος, πιθανά σαν απάντηση αντιρρόπησης του υψηλότερου ρυθμού οστεοκλαστογένεσης. Από την γονιδιακή ανάλυση των πολυμορφισμών A986S, R990G και Q1011E του CaSR, καταγράφηκε συσχέτιση μόνο του A986S με την ΙΥΑ στα παιδιά της μελέτης. Συμπερασματικά οι ασθενείς της μελέτης μας φαίνεται να έχουν φυσιολογική οστική παραγωγή, αλλά αυξημένη οστική απορρόφηση, που βελτιώθηκε μετά την παρέμβαση. Βρέθηκε συσχέτιση μόνο του πολυμορφισμού A986S του CaSR με την ΙΥΑ. Θεωρούμε χρήσιμη την εκτίμηση των βιοχημικών δεικτών οστικής παραγωγής ALP και OC και απορρόφησης β-Crosslaps στον ορό στα παιδιά με ΙΥΑ, ως μια μη επεμβατική μέθοδο ανίχνευσης διαταραχών οστικού μεταβολισμού και παρακολούθησης της αντιμετώπισης της.

scholarly journals The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 479 ◽  
Author(s):  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Ariadna Pielok ◽  
Mateusz Sikora ◽  
Lukas Valihrach ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Nuclear Factor ◽  
Paracrine Signaling ◽  
Receptor Activator ◽  
The Impact

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

scholarly journals Vitamin C Activates Osteoblastogenesis and Inhibits Osteoclastogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 506 ◽  
Author(s):  
Hyeon Choi ◽  
Gyeong-Ji Kim ◽  
Han-Seok Yoo ◽  
Da Song ◽  
Kang-Hyun Chung ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Vitamin C ◽  
Signaling Pathways ◽  
Nuclear Factor Kappa B ◽  
Type I ◽  
Nuclear Factor ◽  
Mineral Density ◽  
Nuclear Factor Kappa ◽  
Ovx Rats ◽  
Receptor Activator

This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/β-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration.

scholarly journals Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts

2017 ◽  
Vol 235 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Ke Ke ◽  
Ok-Joo Sul ◽  
Soo-Wol Chung ◽  
Jae-Hee Suh ◽  
Hye-Seon Choi
Keyword(s):  
Bone Loss ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Receptor Activator ◽  
Recognition Receptor ◽  
Oligomerization Domain

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine–threonine kinases to induce activation of nuclear factor κB (NF-κB), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-κB-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1, and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

scholarly journals Therapeutic efficacy of soluble receptor activator of nuclear factor-κB-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma

2008 ◽  
Vol 7 (10) ◽  
pp. 3389-3398 ◽  
Author(s):  
François Lamoureux ◽  
Gaëlle Picarda ◽  
Julie Rousseau ◽  
Clothilde Gourden ◽  
Séverine Battaglia ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Mouse Model ◽  
Therapeutic Efficacy ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Nonviral Gene Transfer ◽  
Receptor Activator
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