Novel functions for NFκB: inhibition of bone formation.
NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NFκB in the negative regulation of bone formation. In this article, we discuss how NFκB activation affects osteoblast function and bone formation. In particular, we describe how reduced NFκB activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NFκB crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NFκB-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption.
Krum
Susan A
SA
UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Chang
Jia
J
Miranda-Carboni
Gustavo
G
Wang
Cun-Yu
CY
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology; D000099169:Fos-Related Antigen 1
D004958:Estradiol; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; D000099169:Fos-Related Antigen 1