RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production

Lee, Sun-Kyeong; Gardner, Amy; Kalinowski, Judith; Jastrzebski, Sandra; Lorenzo, Joseph

doi:10.1016/j.bone.2005.10.011

Cited by 68 publications

(44 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One is to increase osteoclastic bone resorption, and another is to increase lymphatic channel numbers and presumably lymph flow away from inflamed joints. It remains to be determined if osteoclasts play a significant role in lymphatic vessel formation during development, but the absence of osteoclasts and lymph nodes in mice deficient in RANKL, RANK, or NF-B p50/p52 (4,35) suggests that this merits further study.…”

Section: Discussionmentioning

confidence: 99%

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

Zhang

Guo

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

Zhang

Guo

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…miR-29 Knockdown and Osteoclast Formation-Whole bone marrow was isolated from 6 -8-week-old C57BL/6 mice and plated overnight on a tissue culture plastic plate to limit the amount of stromal cells. The nonadherent population of cells was centrifuged on a Ficoll gradient, to enrich for macrophage precursors (30). These bone marrow-derived macrophages were seeded at 5,000 cells/well in 96-well plates, in ␣-MEM supplemented with 10% FBS in the presence of 30 ng/ml M-CSF.…”

Section: Methodsmentioning

confidence: 99%

miR-29 Promotes Murine Osteoclastogenesis by Regulating Osteoclast Commitment and Migration

Franceschetti

Kessler

Lee

et al. 2013

Journal of Biological Chemistry

Self Cite

112

110

View full text Add to dashboard Cite

Background: miR-29 is a positive regulator of osteoblastogenesis, but its role in osteoclastogenesis is undefined. Results: Expression of all miR-29 family members increased during osteoclastic differentiation. miR-29 knockdown impaired migration, osteoclast commitment, and formation. Six novel miR-29 targets were identified. Conclusion: miR-29 promotes osteoclastogenesis. Significance: These data expand our understanding of osteoclastogenesis, providing insight into miR-29 function in hematopoietic cells and other lineages.

show abstract

“…In the OC lineage, however, inhibition of ROS reduces differentiation and bone resorption (28,29). JNK activation is also required for OC differentiation (30)(31)(32). RANKL activates both ROS and JNK, and these linked pathways contribute both differentiation and apoptotic signals.…”

Section: Figurementioning

confidence: 99%

RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice

Vaira¹,

Alhawagri²,

Anwisye³

et al. 2008

J. Clin. Invest.

121

144

View full text Add to dashboard Cite

Osteoclasts (OCs) function to reabsorb bone and are responsible for the bone loss associated with inflammatory arthritis and osteoporosis. OC numbers are elevated in most disorders of accelerated bone destruction, reflecting altered rates of precursor differentiation and apoptosis. Both of these processes are regulated by the JNK family of MAP kinases. In this study, we have demonstrated that the NF-κB subunit RelA/p65 inhibits JNKmediated apoptosis during a critical period of commitment to the OC phenotype in response to the cytokine RANKL. This RelA/p65-mediated arrest of cell death led to enhanced OC differentiation. Hence, Rela -/-OC precursors displayed prolonged JNK activation in response to RANKL, and this was accompanied by an increase in cell death that prevented efficient differentiation. Although complete blockade of JNK activity inhibits osteoclastogenesis, both short-term blockade in RelA-deficient cultures and suppression of the downstream mediator, Bid rescued apoptosis and differentiation. These antiapoptotic effects were RelA specific, as overexpression of RelA, but not RelB, blocked apoptosis and rescued differentiation in Rela -/-precursors. Thus, RelA blocks a RANKL-induced, apoptotic JNK-Bid pathway, thereby promoting OC differentiation. Consistent with this, mice lacking RelA/p65 in the hematopoietic compartment were shown to have a deficient osteoclastogenic response to RANKL and were protected from arthritis-induced osteolysis. IntroductionOsteoclasts (OCs) are multinucleated cells derived from myeloid bone marrow progenitors that express RANK, the receptor for the key osteoclastogenic cytokine RANKL (1). Increased OC formation and activity is observed in many osteopenic disorders, including postmenopausal osteoporosis, lytic bone metastasis, and rheumatoid arthritis, and leads to pain and structural instability. Osteoblast lineage cells express a membrane-bound form of RANKL, a member of the TNF cytokine family. Like other members of the TNF receptor superfamily, RANK strongly activates the NF-κB pathway.In mammals, the NF-κB family has 5 members: RelA/p65, RelB, c-Rel, NF-κB1/p50, and NF-κB2/p52 (2). In the canonical NF-κB pathway, ligation of RANK activates the inhibitor of IκB kinase (IKK) complex, which phosphorylates NF-κB-associated IκBα, leading to its ubiquitination and proteosomal degradation. These events release NF-κB dimers containing RelA and c-Rel in the cytosol, allowing them to translocate into the nucleus where they enhance transcription of target genes. In the alternative NF-κB pathway, NF-κB-inducing kinase (NIK) and IKKα target p100 for ubiquitination and processing, thereby allowing nuclear translocation of predominantly RelB-containing dimers.The importance of NF-κB in osteoclastogenesis has been highlighted by several mouse models. Mice lacking both NF-κB1 and NF-κB2 have severe osteopetrosis with complete absence of OCs

show abstract

RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production

Cited by 68 publications

References 51 publications

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism

miR-29 Promotes Murine Osteoclastogenesis by Regulating Osteoclast Commitment and Migration

RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice

Contact Info

Product

Resources

About