[Zoledronate regulates osteoclast differentiation and bone resorption in high glucose through p38 MAPK pathway].

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  • Additional Information
    • Source:
      Publisher: Nanfang yi ke da xue xue bao bian ji bu Country of Publication: China NLM ID: 101266132 Publication Model: Print Cited Medium: Print ISSN: 1673-4254 (Print) Linking ISSN: 16734254 NLM ISO Abbreviation: Nan Fang Yi Ke Da Xue Xue Bao Subsets: MEDLINE
    • Publication Information:
      Original Publication: Guangzhou : Nanfang yi ke da xue xue bao bian ji bu, 2005-
    • Subject Terms:
      Bone Resorption* ; Osteoclasts*; Animals ; Cell Differentiation ; Glucose ; MAP Kinase Signaling System ; Mice ; NFATC Transcription Factors ; RANK Ligand ; Zoledronic Acid/pharmacology ; p38 Mitogen-Activated Protein Kinases
    • Abstract:
      Objective: To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process.
      Methods: RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting.
      Results: The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells ( P < 0.05), inhibited the clarity of cytoskeleton and the formation of sealing zones in the osteoclasts. Exposure to high glucose significantly lowered the expressions of p38 MAPK, p-p38 MAPK, NFATc1, CTSK and TRAP, and inhibited osteoclast differentiation and bone absorption ( P < 0.05). Treatment with ZOL obviously suppressed the migration ability of RAW264.7 cells, further reduced the clarity of the cytoskeleton, inhibited the formation of sealing zones of the osteoclasts, lowered the expressions of p38 MAPK, p-p38 MAPK, NFATc1, CTSK, and TRAP ( P < 0.05), and inhibited osteoclast differentiation and bone absorption. Treatment with SB203580 obviously inhibited osteoclast differentiation and bone resorption and the expressions of P38 MAPK, p-p38 MAPK, NFATc1, CTSK and TRAP ( P < 0.05).
      Conclusions: High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.
    • References:
      J Biol Chem. 2019 Oct 18;294(42):15395-15407. (PMID: 31462535)
      PLoS One. 2014 Jan 06;9(1):e84818. (PMID: 24400116)
      Int J Biol Sci. 2016 Jan 01;12(2):235-45. (PMID: 26884720)
      Diabetes Res Clin Pract. 2011 Aug;93(2):166-173. (PMID: 21524811)
      Sci Rep. 2017 Apr 06;7:45964. (PMID: 28382965)
      Calcif Tissue Int. 2017 Feb;100(2):122-132. (PMID: 28180919)
      Phytother Res. 2015 Sep;29(9):1286-1294. (PMID: 26059856)
      Am J Transl Res. 2019 Sep 15;11(9):5417-5437. (PMID: 31632520)
      J Transl Med. 2015 Mar 15;13:91. (PMID: 25889035)
      J Bone Metab. 2019 Aug;26(3):133-143. (PMID: 31555610)
      J Cell Physiol. 2020 Mar;235(3):3022-3032. (PMID: 31541460)
      Biochem Genet. 2020 Jun;58(3):473-489. (PMID: 32274606)
      Mol Cell Endocrinol. 2020 May 15;508:110791. (PMID: 32173349)
      Eur J Pharmacol. 2020 Jan 5;866:172773. (PMID: 31705903)
      Curr Osteoporos Rep. 2015 Oct;13(5):327-35. (PMID: 26254939)
      Am J Pathol. 2013 Dec;183(6):1928-1935. (PMID: 24113454)
      Spine J. 2018 Oct;18(10):1877-1887. (PMID: 29793000)
      J Diabetes Res. 2018 Nov 4;2018:6354787. (PMID: 30525054)
      Int J Mol Med. 2019 Aug;44(2):582-592. (PMID: 31173157)
      Biochem Biophys Res Commun. 2018 Sep 5;503(2):428-435. (PMID: 29649480)
      Endocrinology. 2019 Oct 1;160(10):2339-2352. (PMID: 31504411)
      Mol Cells. 2020 Jan 31;43(1):34-47. (PMID: 31896234)
      Front Endocrinol (Lausanne). 2019 Feb 19;10:85. (PMID: 30837952)
      Mol Med Rep. 2015 Feb;11(2):865-70. (PMID: 25352342)
      J Bone Miner Metab. 2020 Sep;38(5):607-619. (PMID: 32415376)
      Cell Chem Biol. 2019 Jul 18;26(7):926-935.e6. (PMID: 31031140)
      Expert Opin Biol Ther. 2019 Sep;19(9):937-948. (PMID: 31079501)
      Acta Biomater. 2019 Jan 15;84:402-413. (PMID: 30508657)
      Life Sci. 2019 Jul 1;228:208-214. (PMID: 31055087)
      Biochem Biophys Res Commun. 2018 Nov 10;505(4):1195-1202. (PMID: 30322621)
      Exp Clin Endocrinol Diabetes. 2019 Jan;127(1):68-75. (PMID: 27355188)
      J Cell Physiol. 2017 Dec;232(12):3611-3621. (PMID: 28138960)
    • Contributed Indexing:
      Keywords: high glucose; osteoclast; p38 mitogen-activated kinase; zoledronate
    • Accession Number:
      0 (NFATC Transcription Factors)
      0 (RANK Ligand)
      6XC1PAD3KF (Zoledronic Acid)
      EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20201029 Date Completed: 20201102 Latest Revision: 20201104
    • Publication Date:
      20240829
    • Accession Number:
      PMC7606243
    • Accession Number:
      10.12122/j.issn.1673-4254.2020.10.09
    • Accession Number:
      33118518