Molecular mechanisms of BMP-induced bone formation: Cross-talk between BMP and NF-κB signaling pathways in osteoblastogenesis

Jimi, Eijiro; Hirata, Shizu; Shin, Masashi; Yamazaki, Masato; Fukushima, Hidefumi

doi:10.1016/j.jdsr.2009.10.003

Cited by 38 publications

(37 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results suggest that LLLI affects osteoblast differentiation by stimulating multiple steps that are required for the differentiation of osteoblast progenitors into mature osteoblasts. Smad1/5/8 signaling is now generally accepted to be a downstream effector of the BMP signaling pathway and is thus fundamental for osteoblastic differentiation in response to BMP [Katagiri et al, 2008;Jimi et al, 2010]. Therefore, increasing BMP2-induced Smad phosphorylation by laser irradiation might contribute to the phenomenon of increased BMP2-induced osteoblast differentiation after laser treatment.…”

Section: Discussionmentioning

confidence: 99%

Low‐level laser irradiation enhances BMP‐induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway

Hirata

Kitamura

Fukushima

et al. 2010

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Low-level laser irradiation (LLLI) has been shown to induce bone formation and osteoblast differentiation both in vivo and in vitro. However, the molecular mechanism by which LLLI stimulates osteoblast differentiation is still unclear. The aim of the present study was to examine whether Ga-Al-As laser irradiation could enhance BMP2-induced alkaline phosphatase (ALP) activity in C2C12 cells. Laser irradiation at 0.5 W for 20 min enhanced BMP2-induced ALP activity. Laser treatment alone did not affect ALP activity. To exclude the effect of pH or temperature changes during irradiation, we shortened the exposure time to 2 min, with various levels of laser power. At 2.5 W, irradiation stimulated BMP2-induced ALP activity but not cell proliferation, whereas 1 or 5 W laser power did not induce any significant effects. Irradiation stimulated BMP2-induced phosphorylation of Smad1/5/8 and BMP2 expression, but had no effect on the expression of inhibitory Smads 6 and 7, BMP4, or insulin-like growth factor 1. Laser irradiation enhanced Smad-induced Id1 reporter activity as well as expression of bone morphogenetic protein (BMP)-induced transcription factors such as Id1, Osterix, and Runx2. Laser irradiation also stimulated BMP-induced expressions of type I collagen, osteonectin, and osteocalcin mRNA, markers of osteoblasts. This enhancement of BMP2-induced ALP activity and Smad phosphorylation by laser irradiation was also observed in primary osteoblasts. These results suggest that LLLI accelerates the differentiation of BMP-induced osteoblasts by stimulating the BMP/Smad signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Low‐level laser irradiation enhances BMP‐induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway

Hirata

Kitamura

Fukushima

et al. 2010

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The connection between NF-κB and OBs stems from initial observations that inflammation, and in particular TNFα, inhibits bone formation in vivo and in vitro [39,40]. Li et al [41] then showed that TNFα-and TNFR1-deficient mice have increased basal bone mass in vivo and increased OB differentiation in vitro.…”

Section: Nf-κb In Obsmentioning

confidence: 99%

Role of NF-κB in the skeleton

2010

View full text Add to dashboard Cite

Since the discovery that deletion of the NF-κB subunits p50 and p52 causes osteopetrosis in mice, there has been considerable interest in the role of NF-κB signaling in bone. NF-κB controls the differentiation or activity of the major skeletal cell types -osteoclasts, osteoblasts, osteocytes and chondrocytes. However, with five NF-κB subunits and two distinct activation pathways, not all NF-κB signals lead to the same physiologic responses. In this review, we will describe the roles of various NF-κB proteins in basal bone homeostasis and disease states, and explore how NF-κB inhibition might be utilized therapeutically.

show abstract

“…The differentiation pathway for mesenchymal stem cells is regulated by tissue-specific transcription factors. For example, in mesenchymal stem cells the chondroblastic lineage is induced by sex-determining region Y (SRY)-box 9, the myoblastic lineage by myogenic differentiation 1 family proteins, the adipoblastic lineage by peroxisome proliferator-activated receptor γ, and the osteoblastic lineage by runt-related transcription factor 2 (RUNX2) (3).…”

Section: Introductionmentioning

confidence: 99%