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10.3892/ijmm.2016.2582 http://scihub22266oqcxt.onion/10.3892/ijmm.2016.2582 C4899021!4899021!27176567     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Int+J+Mol+Med 2016 ; 38 (1): 139-47 Nephropedia Template TP {{tp|p=27176567|t=2016. Zoledronic acid suppresses transforming growth factor-?-induced fibrogenesis by human gingival fibroblasts |pdf=|usr=}}{{27176567}} gab.com Text Zoledronic acid suppresses transforming growth factor- -induced fibrogenesis by human gingival fibroblasts JO: Int J Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=27176567 #FOAvip Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-? (TGF-?)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-?-induced promotion of cell viability, ii) the TGF-?-induced expression of MF markers such as ?-smooth muscle actin (?-SMA) and type I collagen, iii) the TGF-?-induced migratory activity of hGFs and iv) the expression level of TGF-? type I receptor on the surfaces of hGFs, as well as the TGF-?-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-?-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. Twit Text FOAVip Zoledronic acid suppresses transforming growth factor- -induced fibrogenesis by human gingival fibroblasts ????Int J Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=27176567 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27176567 #FOAvip English Wikipedia <ref>{{Cite pmid|27176567}}</ref> Zoledronic acid suppresses transforming growth factor-?-induced fibrogenesis by human gingival fibroblasts #MMPMID27176567 KOMATSU Y; IBI M; CHOSA N; KYAKUMOTO S; KAMO M; SHIBATA T; SUGIYAMA Y; ISHISAKI A Int J Mol Med 2016[Jul]; 38 (1): 139-47 PMID27176567show ga Bisphosphonates (BPs) are analogues of pyro-phosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-? (TGF-?)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF-?-induced promotion of cell viability, ii) the TGF-?-induced expression of MF markers such as ?-smooth muscle actin (?-SMA) and type I collagen, iii) the TGF-?-induced migratory activity of hGFs and iv) the expression level of TGF-? type I receptor on the surfaces of hGFs, as well as the TGF-?-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF-?-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad-dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level. äZoledronic acid suppresses transforming growth factor-?-induced fibrog(epmc).pdf DeepDyve Pubget Overpricing