NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB

Eijiro Jimi, Hidefumi Fukushima

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.

Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalClinical calcium
Volume26
Issue number2
Publication statusPublished - Feb 1 2016
Externally publishedYes

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Bone Diseases
Squamous Cell Carcinoma
Osteoclasts
Osteogenesis
Osteopetrosis
Bone and Bones
Periodontitis
Mouth Neoplasms
Therapeutics
Bone Resorption
Cytoplasmic and Nuclear Receptors
Jaw
Osteoblasts
Osteoporosis
Arthritis
Carcinogenesis
Animal Models
Ligands
Genes
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB. / Jimi, Eijiro; Fukushima, Hidefumi.

In: Clinical calcium, Vol. 26, No. 2, 01.02.2016, p. 298-304.

Research output: Contribution to journalReview article

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