Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL–RANK signaling system

Tanaka, Sakae; Nakamura, Kozo; Takahasi, Naoyuki; Suda, Toshio

doi:10.1111/j.0105-2896.2005.00327.x

Cited by 289 publications

(277 citation statements)

References 225 publications

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“…It has been reported that Pax5-deficient mice exhibit osteopenia (25), a pathological condition in which osteoclasts are likely to be involved (39). Although Pax5 was detected only in the B cell lineage, and not in bone marrow macrophages nor in osteoclasts (40), the report nonetheless suggests that Pax5 or its related Pax family members may play a role in bone metabolism.…”

Section: Pax6 Expression During Rankl-induced Osteoclastogenesis-mentioning

confidence: 76%

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

Kogawa¹,

Hisatake

Atkins

et al. 2013

Journal of Biological Chemistry

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Background: Negative regulation of osteoclast differentiation is critical for suppression of pathological bone destruction. Results: Pax6 is induced by RANKL in osteoclasts and attenuates osteoclast differentiation via blocking TRAP gene expression. Conclusion: Pax6 functions together with its co-receptor to suppress TRAP gene expression and osteoclastogenesis. Significance: This study provides a new aspect for investigating the molecular targets linked to physiological bone resorption.

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Section: Pax6 Expression During Rankl-induced Osteoclastogenesis-mentioning

confidence: 76%

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

Kogawa¹,

Hisatake

Atkins

et al. 2013

Journal of Biological Chemistry

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“…(1,2) The imbalance between osteoblast and osteoclast activity underlies various bone and joint diseases, such as osteoporosis and rheumatoid arthritis. (3)(4)(5)(6) Osteoclasts are multinucleated giant cells that are polarized and resorb bone through specialized machinery so as to attach to mineralized matrix and degrade it. The differentiation of monocyte/ macrophage-lineage precursor cells into mature osteoclasts is induced by the tumor necrosis factor (TNF) family cytokine receptor activator of NF-kB ligand (RANKL) together with colonystimulating factor (M-CSF), and provides an activating signal as well as survival signals to osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B–mediated vesicle transport

Shirakawa

Nakamura

Masuda

et al. 2012

Journal of Bone and Mineral Research

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Class IA phosphatidylinositol 3-kinases (PI3Ks) are activated by growth factor receptors and regulate a wide range of cellular processes. In osteoclasts, they are activated downstream of a v b 3 integrin and colony-stimulating factor-1 receptor (c-Fms), which are involved in the regulation of bone-resorbing activity. The physiological relevance of the in vitro studies using PI3K inhibitors has been of limited value, because they inhibit all classes of PI3K. Here, we show that the osteoclast-specific deletion of the p85 genes encoding the regulatory subunit of the class IA PI3K results in an osteopetrotic phenotype caused by a defect in the bone-resorbing activity of osteoclasts. Class IA PI3K is required for the ruffled border formation and vesicular transport, but not for the formation of the sealing zone. p85a/b doubly deficient osteoclasts had a defect in macrophage colony-stimulating factor (M-CSF)-induced protein kinase B (Akt) activation and the introduction of constitutively active Akt recovered the bone-resorbing activity. Thus, the class IA PI3K-Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases. ß

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“…It also binds to activated RANK (9), thereby recruiting TRAF6 and Grb2-associated binder 2 (Gab2) followed by phosphorylation of I B␣ and JNK (10), which ultimately lead to respective activation of the transcription factors NF-B and AP-1 (2,11,12).…”

mentioning

confidence: 99%

The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo

Kim

Zhang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL–RANK signaling system

Cited by 289 publications

References 225 publications

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

The Paired-box Homeodomain Transcription Factor Pax6 Binds to the Upstream Region of the TRAP Gene Promoter and Suppresses Receptor Activator of NF-κB Ligand (RANKL)-induced Osteoclast Differentiation

Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B–mediated vesicle transport

The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo

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