Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology

2001 ◽  
Vol 79 (5-6) ◽  
pp. 243-253 ◽  
Author(s):  
Lorenz C. Hofbauer ◽  
Armin E. Heufelder
Keyword(s):  
Cell Biology ◽  
Nuclear Factor Κb ◽  
Bone Cell ◽  
Nuclear Factor ◽  
Receptor Activator

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 Interleukin-6 Inhibits Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclastogenesis by Diverting Cells into the Macrophage Lineage: Key Role of Serine727 Phosphorylation of Signal Transducer and Activator of Transcription 3

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3688-3697 ◽  
Author(s):  
Laurence Duplomb ◽  
Marc Baud’huin ◽  
Céline Charrier ◽  
Martine Berreur ◽  
Valérie Trichet ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Signal Transducer ◽  
Blood Monocytes ◽  
Receptor Activator ◽  
Few Data ◽  
Macrophage Lineage

Osteoclasts are bone-resorptive cells that differentiate from hematopoietic precursors upon receptor activator of nuclear factor κB ligand (RANKL) activation. Previous studies demonstrated that IL-6 indirectly stimulates osteoclastogenesis through the production of RANKL by osteoblasts. However, few data described the direct effect of IL-6 on osteoclasts. To investigate this effect, we used several models: murine RAW264.7 cells, mouse bone marrow, and human blood monocytes. In the three models used, the addition of IL-6 inhibited RANKL-induced osteoclastogenesis. Furthermore, IL-6 decreased the expression of osteoclast markers and up-modulated macrophage markers. To elucidate this inhibition, signal transducer and activator of transcription (STAT) 3, the main signaling molecule activated by IL-6, was analyzed. Addition of two STAT3 inhibitors completely abolished RANKL-induced osteoclastogenesis, revealing a key role of STAT3. We demonstrated that a basal level of phosphorylated-STAT3 on Serine727 associated with an absence of phosphorylation on Tyrosine705 is essential for osteoclastogenesis. Furthermore, a decrease of Serine727 phosphorylation led to an inhibition of osteoclast differentiation, whereas an increase of Tyrosine705 phosphorylation upon IL-6 stimulation led to the formation of macrophages instead of osteoclasts. In conclusion, we showed for the first time that IL-6 inhibits RANKL-induced osteoclastogenesis by diverting cells into the macrophage lineage, and demonstrated the functional role of activated-STAT3 and its form of phosphorylation in the control of osteoclastogenesis.

scholarly journals Parathyroid Hormone-Related Protein (PTHrP) Accelerates Soluble RANKL Signals for Downregulation of Osteogenesis of Bone Mesenchymal Stem Cells

2019 ◽  
Vol 8 (6) ◽  
pp. 836 ◽  
Author(s):  
Jeevithan Elango ◽  
Saeed Ur Rahman ◽  
Yves Henrotin ◽  
José Eduardo Maté Sánchez de Val ◽  
Bin Bao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Parathyroid Hormone ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Related Protein ◽  
Bone Mesenchymal Stem Cells ◽  
Parathyroid Hormone Related Protein ◽  
Receptor Activator

A recent study reported the expression of receptor activator of nuclear factor-κB (RANK) in mesenchymal stem cells (MSCs) surface that negatively regulates osteogenesis of MSCs. Empirical evidence from the previous study confirmed the role of parathyroid hormone-related protein (PTHrP) in osteoblastogenesis. However, it is necessary to understand the paracrine role of PTHrP and RANKL for osteogenesis in order to explore the hidden secrets in bone biology. Considering the above concept, paracrine cues of soluble-receptor activator of nuclear factor-κB ligand (sRANKL) and PTHrP in osteogenic differentiation of MSCs were investigated. Our results confirmed that sRANKL increased the expression of surface-RANK in MSCs at the earlier stage of osteogenesis, which was downregulated later in differentiated MSCs. In contrast, RANKL expression was low at the earlier stage of MSCs proliferation and high at the differentiation stage of MSCs, which may play a fundamental role in osteoclast formation. sRANKL downregulated osteogenesis of MSCs by decreasing progressive ankylosis (ANK) protein expression while PTHrP upregulated the osteogenic exploitive effect of sRANKL. Interestingly, when they were co-cultured with MSCs, T-lymphocytes expressed high membrane-RANKL levels that contribute to osteogenesis inhibition during MSC differentiation. Thus, our results disclose that sRANKL treatment downregulates osteogenesis of MSCs by increasing RANK expression at the earlier stage of differentiation and by inhibiting ANK. Further, we demonstrated that PTHrP accelerated the downregulating osteogenic effect of sRANKL.

The role of serum osteoprotegerin and receptor–activator of nuclear factor-κB ligand in metabolic bone disease of women after obesity surgery

2015 ◽  
Vol 34 (6) ◽  
pp. 655-661 ◽  
Author(s):  
José A. Balsa ◽  
Christian Lafuente ◽  
Jesús M. Gómez-Martín ◽  
Julio Galindo ◽  
Roberto Peromingo ◽  
...  
Keyword(s):  
Obesity Surgery ◽  
Bone Disease ◽  
Metabolic Bone Disease ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Metabolic Bone ◽  
Receptor Activator

The role of Mac-1 (CD11b/CD18) in osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand

FEBS Letters ◽  
2008 ◽  
Vol 582 (21-22) ◽  
pp. 3243-3248 ◽  
Author(s):  
Hidetaka Hayashi ◽  
Ken-ichi Nakahama ◽  
Takahiro Sato ◽  
Takehiko Tuchiya ◽  
Yasuyuki Asakawa ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals Role of Prostaglandin E in Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Osteoblasts Induced by Cell Adhesion to Bone Marrow B-lymphocytes

2009 ◽  
Vol 55 (5) ◽  
pp. 832-837 ◽  
Author(s):  
Michiko Hirata ◽  
Suguru Harada ◽  
Chiho Matsumoto ◽  
Morichika Takita ◽  
Chisato Miyaura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Lymphocytes ◽  
Nuclear Factor Κb ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

scholarly journals Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 336-345 ◽  
Author(s):  
Sangmi Ock ◽  
Wang Soo Lee ◽  
Jihyun Ahn ◽  
Hyun Min Kim ◽  
Hyun Kang ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypertrophic Response ◽  
Age Related ◽  
Receptor Activator ◽  
Phosphoinositide 3 Kinase ◽  
Cultured Cardiomyocytes

Abstract IGF-1 receptor (IGF-1R) signaling is implicated in cardiac hypertrophy and longevity. However, the role of IGF-1R in age-related cardiac remodeling is only partially understood. We therefore sought to determine whether the deletion of the IGF-1R in cardiomyocytes might delay the development of aging-associated myocardial pathologies by examining 2-year-old male cardiomyocyte-specific IGF-1R knockout (CIGF1RKO) mice. Aging was associated with the induction of IGF-1R expression in hearts. Cardiomyocytes hypertrophied with age in wild-type (WT) mice. In contrast, the cardiac hypertrophic response associated with aging was blunted in CIGF1RKO mice. Concomitantly, fibrosis was reduced in aged CIGF1RKO compared with aged WT hearts. Expression of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and receptor activator of nuclear factor-κB ligand was increased in aged WT hearts, but this increase was attenuated in aged CIGF1RKO hearts. Phosphorylation of Akt was increased in aged WT, but not in aged CIGF1RKO, hearts. In cultured cardiomyocytes, IGF-1 induced senescence as demonstrated by increased senescence-associated β-galactosidase staining, and a phosphoinositide 3-kinase inhibitor inhibited this effect. Furthermore, inhibition of phosphoinositide 3-kinase significantly prevented the increase in IL-1α, IL-1β, receptor activator of nuclear factor-κB ligand, and p21 protein expression by IGF-1. These data reveal an essential role for the IGF-1-IGF-1R-Akt pathway in mediating cardiomyocyte senescence.

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