Osteoclast Differentiation Requires Ascorbic Acid

Ragab, Ashraf; Lavish, Sandra A.; Banks, Michael; Goldberg, Victor M.; Greenfield, Edward M.

doi:10.1359/jbmr.1998.13.6.970

Cited by 40 publications

(23 citation statements)

References 54 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The medium was changed every 3 days. After 5 days, the cells were stained for TRAP and the number of TRAP + -MNCs was determined as previously described (51).…”

Section: Methodsmentioning

confidence: 99%

A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells

Miura¹,

Chen²,

Allen³

et al. 2004

J. Clin. Invest.

228

148

View full text Add to dashboard Cite

Caspase-3 is a critical enzyme for apoptosis and cell survival. Here we report delayed ossification and decreased bone mineral density in caspase-3-deficient (Casp3 -/-and Casp3 +/-) mice due to an attenuated osteogenic differentiation of bone marrow stromal stem cells (BMSSCs). The mechanism involved in the impaired differentiation of BMSSCs is due, at least partially, to the overactivated TGF-β/Smad2 signaling pathway and the upregulated expressions of p53 and p21 along with the downregulated expressions of Cdk2 and Cdc2, and ultimately increased replicative senescence. In addition, the overactivated TGF-β/Smad2 signaling may result in the compromised Runx2/Cbfa1 expression in preosteoblasts. Furthermore, we demonstrate that caspase-3 inhibitor, a potential agent for clinical treatment of human diseases, caused accelerated bone loss in ovariectomized mice, which is also associated with the overactivated TGF-β/Smad2 signaling in BMSSCs. This study demonstrates that caspase-3 is crucial for the differentiation of BMSSCs by influencing TGF-β/Smad2 pathway and cell cycle progression.

show abstract

“…The medium was changed every 3 days. After 5 days, the cells were stained for TRAP and the number of TRAP + -MNCs was determined as previously described (51).…”

Section: Methodsmentioning

confidence: 99%

A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells

Miura¹,

Chen²,

Allen³

et al. 2004

J. Clin. Invest.

228

148

View full text Add to dashboard Cite

show abstract

“…(5) The number of TRAP ϩ multinuclear cells (MNCs) containing three or more nuclei was determined as previously described. (44) Previously, we have shown that the TRAP ϩ MNCs that are induced by conditioned media from marrow cells incubated with cpTi particles form substantial amounts of resorption lacunae. (5) Cytokine concentrations in the conditioned media .…”

Section: In Vitro Experimentsmentioning

confidence: 97%

Adherent Endotoxin on Orthopedic Wear Particles Stimulates Cytokine Production and Osteoclast Differentiation

Seabold

Kaar

et al. 2001

Journal of Bone and Mineral Research

Self Cite

211

207

View full text Add to dashboard Cite

Aseptic loosening of orthopedic implants is thought to be caused primarily by osteoclast differentiation induced by bone resorptive cytokines produced in response to phagocytosis of implant-derived wear particles. This study examined whether adherent endotoxin on the wear particles is responsible for inducing osteoclast differentiation as well as production of interleukin-1␤ (IL-1␤), IL-6, and tumor necrosis factor ␣ (TNF-␣). Removal of adherent endotoxin almost completely inhibited the responses to titanium (Ti) particles by both murine marrow cells and human peripheral blood monocytes. In vivo experiments showed that endotoxin removal reduced particle-induced osteolysis by 50 -70%. Addition of lipopolysaccharide (LPS) to the "endotoxin-free" particles restored their ability to induce cytokine production and osteoclast differentiation in vitro. Moreover, marrow cells from mice that are hyporesponsive to endotoxin because of mutation of Toll-like receptor 4 induced significantly less cytokine production and osteoclast differentiation in response to Ti particles with adherent endotoxin than did marrow cells from normoresponsive mice. This mutation also resulted in significantly less particle-induced osteolysis in vivo. Taken

show abstract

“…ST2 cells (passage were plated at 8 × 10 4 cells/ cm 2 in 24 well plates. Twenty-four hours later (day 0 of differentiation) Balb/c marrow cells were added at 2.1 × 10 4 cells/cm 2 to the ST2 cell cultures in MEM (Invitrogen, Carlsbad, CA), 10% (v/v) FBS, 1% (v/v) non-essential amino acids, antibiotic/antimycotic, 7 × 10 -3 M ascorbic acid (Invitrogen), 1 × 10 -7 M dexamethasone, 1 × 10 -5 M, vitamin D 3 (Biomol, Plymouth Meeting, PA) 100 ng/ml biotin, 1.36 ug/ml vitamin B12, and 299 ng/ml lipoic acid [37]. Medium was changed every three days through day 9.…”

Section: Osteoclast Culture Without Stromal Cell Additionmentioning

confidence: 99%

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

Gingery

Bradley

Pederson

et al. 2008

Experimental Cell Research

159

118

View full text Add to dashboard Cite

To better understand the roles of TGF-β in bone metabolism, we investigated osteoclast survival in response TGF-β and found that TGF-β inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-β receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-β treatment. Since osteoclast survival involves MEK, AKT, and NFκB activation, we examined TGF-β effects on activation of these pathways and observed rapid phosphorylation of MEK, AKT, IKK, IκB, and NFκB. The timing of activation coincided with SMAD activation and dominant negative SMAD expression did not inhibit NFκB activation, indicating that kinase pathway activation is independent of SMAD signaling. Inhibition of TAK1, MEK, AKT, NIK, IKK, or NFκB repressed TGF-β-mediated osteoclast survival. Adenoviral-mediated TAK1 or MEK inhibition eliminated TGF-β-mediated kinase pathway activation and constitutively active AKT expression overcame apoptosis induction following MEK inhibition. TAK1/MEK activation induces pro-survival BclX L expression and TAK1/MEK and SMAD pathway activation induces pro-survival Mcl-1 expression. These data show that TGF-β-induced NFκB activation is through TAK1/MEK-mediated AKT activation, which is essential for TGF-β to support of osteoclast survival.

show abstract

Osteoclast Differentiation Requires Ascorbic Acid

Cited by 40 publications

References 54 publications

A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells

A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells

Adherent Endotoxin on Orthopedic Wear Particles Stimulates Cytokine Production and Osteoclast Differentiation

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

Contact Info

Product

Resources

About