Advanced Glycation Endproducts Stimulate Interleukin-6 Production by Human Bone-Derived Cells

Takagi, Masao; Kasayama, Soji; Yamamoto, Takehisa; Mizutani, Takashi; Hashimoto, Kunihiko; Yamamoto, Hiroyasu; Sato, Bunzo; Okada, Shintaro; Kishimoto, Tadamitsu

doi:10.1359/jbmr.1997.12.3.439

Cited by 99 publications

(64 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…AGEs have previously been reported to stimulate activation of NF-κB (46). When NF-κB was inhibited, apoptosis in response to CML-collagen was further enhanced.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Alikhani

Boyd

et al. 2007

Bone

321

220

View full text Add to dashboard Cite

We have previously shown that diabetes significantly enhances apoptosis of osteoblastic cells in vivo and that the enhanced apoptosis contributes to diabetes impaired new bone formation. A potential mechanism is enhanced apoptosis stimulated by advanced glycation endproducts (AGEs). To investigate this further, an advanced glycation product, carboxymethyl lysine modified collagen (CML-collagen) was injected in vivo and stimulated a 5 fold increase in calvarial periosteal cell apoptosis compared to unmodified collagen. It also induced apoptosis in primary cultures of human or neonatal rat osteoblastic cells or MC-3T3-E1 cells in vitro. Moreover, the apoptotic effect was largely mediated through RAGE receptor. CML-collagen increased p38 and JNK activity 3.2 and 4.4 fold, respectively. Inhibition of p38 and JNK reduced CML-collagen stimulated apoptosis by 45% and 59% and by 90% when used together (P<0.05). The predominant apoptotic pathway induced by CML-collagen involved caspase-8 activation of caspase-3 and was independent of NF-κB activation. When osteoblastic cells were exposed to a long-term low dose incubation with CMLcollagen there was a higher degree of apoptosis compared to short term incubation. In more differentiated osteoblastic cultures apoptosis was enhanced even further. These results indicate that advanced glycation endproducts, which accumulate in diabetic and aged individuals may promote apoptosis of osteoblastic cells and contribute to deficient bone formation.

show abstract

“…AGEs have previously been reported to stimulate activation of NF-κB (46). When NF-κB was inhibited, apoptosis in response to CML-collagen was further enhanced.…”

Section: Discussionmentioning

confidence: 96%

“…Studies in soft tissue wounds indicate that diabetic mice have increased levels of apoptosis, which may interfere with the capacity for wound healing (11,32,46). Thus, diabetes may have a general effect of increasing apoptosis of matrix producing cells, which limits the repair of injured hard or soft connective tissue.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Alikhani

Boyd

et al. 2007

Bone

321

220

View full text Add to dashboard Cite

show abstract

“…One oxidative stress response, production of AGEs, is considered a nonmicrobial inflammatory factor. Takagi et al 22) reported that AGEs promote expression of IL-6 in human bone-derived cells. AGEs have been considered to induce inflammatory reaction in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Effects of High Glucose for Hard Tissue Formation on Type II Diabetes Model Rat Bone Marrow Cells In Vitro

Okuda

Taguchi

Takahashi

et al. 2015

J. Hard Tissue Biology.

View full text Add to dashboard Cite

Diabetes mellitus (DM) is one of the main etiologies and risk factors for periodontal disease, and is an important concern in periodontal medicine. It has been reported that high glucose concentrations mediate proliferation, differentiation and production of inflammatory cytokines on mesenchymal cells, but there are few reports on periodontal regenerative therapy in type II DM patients. The aim of this study was to examine the biological effects of high glucose conditions on GK rat (type II model) bone marrow mesenchymal cells (GK rat BMMSC). Cell culture experiments were performed with GK rat BMMSC. The effects of glucose at four concentrations (5.5, 8, 12 and 24 mM) were determined by examining cell proliferation, differentiation and production of inflammatory cytokines; the latter three concentrations are higher than the normal physiological glucose concentration, represented by 5.5 mM. High concentrations of glucose promoted proliferation and inhibited hard tissue differentiation and calcification of GK rat BMMSC. Differentiation correlated inversely with the expression of inflammatory cytokines, represented by IL-6. Our data suggest that high extracellular glucose concentrations promote proliferation and inhibit hard tissue differentiation and calcification in periodontal regeneration by causing an inflammatory response dependent on cytokines including IL-6.

show abstract

“…Evidence for the indirect pathway of AGE-induced cellular proliferation is that AGE induces several cytokines or growth factors that use the JAK\STAT signalling pathway [17][18][19][20]. Additionally, JAK\STAT has been shown to contribute to smooth-muscle cell proliferation induced by platelet-derived growth factor and angiotensin II [38].…”

Section: Discussionmentioning

confidence: 99%

“…First, this pathway is activated by several AGE-induced cytokines or growth factors, such as interleukin 6 [17], insulin-like growth factor I [18], epidermal growth factor [19] and platelet-derived growth factor [20]. Secondly, JAK\STAT is also activated by growth hormone and angiotensin II, which have been implicated in the pathogenesis of DN [21,22].…”

Section: Introductionmentioning

confidence: 99%

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

Huang

Guh

Hung

et al. 1999

Biochemical Journal

View full text Add to dashboard Cite

Advanced glycation end product (AGE) is important in the pathogenesis of diabetic nephropathy, which is characterized by cellular hypertrophy/hyperplasia leading to renal fibrosis. However, the signal transduction pathways of AGE remain poorly understood. The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been associated with cellular proliferation in some extra-renal cells. Because interstitial fibroblast proliferation might be important in renal fibrosis, we studied the role of the JAK/STAT pathway in NRK-49F (normal rat kidney fibroblast) cells cultured in AGE/BSA and non-glycated BSA. We showed that AGE dose-dependently (10-200 μg/ml) increased cellular mitogenesis in NRK-49F cells at 5 and 7 days. However, cellular mitogenesis was unaffected by the simultaneous presence of BSA. Regarding the JAK/STAT pathway, AGE (100 μg/ml) induced tyrosine phosphorylation of JAK2 (but not JAK1, JAK3 or TYK2) at 15-60 min; it also induced the tyrosine phosphorylation of STAT1 and STAT3 at 1-2 h and 0.5-4 h respectively. Being a transcription factor, AGE also increased the DNA-binding activities of STAT1 and STAT3 AG-490 (a specific JAK2 inhibitor) (5 μM) inhibited tyrosine phosphorylation of JAK2 and the DNA-binding activities of STAT1 and STAT3. The same results were obtained by using specific ‘decoy’ oligodeoxynucleotides (ODNs) that prevented STAT1 and STAT3 from binding to DNA. Meanwhile, the STAT1 or STAT3 decoy ODN and AG-490 were effective in reversing AGE-induced cellular mitogenesis. We concluded that the JAK2-STAT1/STAT3 signal transduction pathway is necessary for AGE-induced cellular mitogenesis in NRK-49F cells.

show abstract

Advanced Glycation Endproducts Stimulate Interleukin-6 Production by Human Bone-Derived Cells

Cited by 99 publications

References 52 publications

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Effects of High Glucose for Hard Tissue Formation on Type II Diabetes Model Rat Bone Marrow Cells In Vitro

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

Contact Info

Product

Resources

About