For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
Inviting an author to review:
The Health Effects of Indoor Air Pollution
Find an author and click ‘Invite to review selected article’ near their name.
Search for authorsSearch for similar articles
2
views
42
references
 Top references
cited by
13
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      332
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Trelagliptin stimulates osteoblastic differentiation by increasing runt-related transcription factor 2 (RUNX2): a therapeutic implication in osteoporosis

      research-article
      Author(s): a , b , a , a , a
      Publication date (Electronic, pub):
      Publication date (Electronic, collection):
      Journal: Bioengineered
      Publisher: Taylor & Francis
      Keywords: Osteoporosis, Trelagliptin, osteoblastic differentiation, RUNX2, AMPK, MC3T3-E1

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          Osteoporosis, an aging-associated bone metabolic disease, is affecting millions of people worldwide. The deregulated process of osteoblastic differentiation has been linked with the progression of osteoporosis. Trelagliptin is a long-acting inhibitor of DPP-4 used for the management of type 2 diabetes mellitus. However, it is unknown whether Trelagliptin possesses a beneficial effect in osteoblastic differentiation. Interestingly, we found that treatment with Trelagliptin enhanced differentiation and promoted the mineralization of MC3T3-E1 cells. Firstly, Trelagliptin increased the activity of alkaline phosphatase (ALP) and promoted osteoblastic calcium deposition. Additionally, treatment with Trelagliptin upregulated ALP, osteocalcin (OCN), osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). Notably, Trelagliptin increased RUNX2, a major regulator of osteoblastic differentiation. Mechanistically, Trelagliptin upregulated the levels of p-AMPKα. Blockage of AMPK with compound C abolished the effects of Trelagliptin in RUNX2 and osteoblastic differentiation, suggesting the involvement of AMPK. Our findings suggest that Trelagliptin might possess a potential for the treatment of osteoporosis.

          Graphical Abstract

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts.

          T Komori, H Yagi, S Nomura … (1997)
          A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.
          Article 0 comments Cited 256 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2

            Toshihisa Komori (2019)
            Runx2 is essential for osteoblast differentiation and chondrocyte maturation. During osteoblast differentiation, Runx2 is weakly expressed in uncommitted mesenchymal cells, and its expression is upregulated in preosteoblasts, reaches the maximal level in immature osteoblasts, and is down-regulated in mature osteoblasts. Runx2 enhances the proliferation of osteoblast progenitors by directly regulating Fgfr2 and Fgfr3. Runx2 enhances the proliferation of suture mesenchymal cells and induces their commitment into osteoblast lineage cells through the direct regulation of hedgehog (Ihh, Gli1, and Ptch1), Fgf (Fgfr2 and Fgfr3), Wnt (Tcf7, Wnt10b, and Wnt1), and Pthlh (Pthr1) signaling pathway genes, and Dlx5. Runx2 heterozygous mutation causes open fontanelle and sutures because more than half of the Runx2 gene dosage is required for the induction of these genes in suture mesenchymal cells. Runx2 regulates the proliferation of osteoblast progenitors and their differentiation into osteoblasts via reciprocal regulation with hedgehog, Fgf, Wnt, and Pthlh signaling molecules, and transcription factors, including Dlx5 and Sp7. Runx2 induces the expression of major bone matrix protein genes, including Col1a1, Spp1, Ibsp, Bglap2, and Fn1, in vitro. However, the functions of Runx2 in differentiated osteoblasts in the expression of these genes in vivo require further investigation.
            Article 0 comments Cited 209 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development.

              Florian Otto, Anders P Thornell, Tessa Crompton … (1997)
              We have generated Cbfa1-deficient mice. Homozygous mutants die of respiratory failure shortly after birth. Analysis of their skeletons revealed an absence of osteoblasts and bone. Heterozygous mice showed specific skeletal abnormalities that are characteristic of the human heritable skeletal disorder, cleidocranial dysplasia (CCD). These defects are also observed in a mouse Ccd mutant for this disease. The Cbfa1 gene was shown to be deleted in the Ccd mutation. Analysis of embryonic Cbfa1 expression using a lacZ reporter gene revealed strong expression at sites of bone formation prior to the earliest stages of ossification. Thus, the Cbfa1 gene is essential for osteoblast differentiation and bone formation, and the Cbfa1 heterozygous mouse is a paradigm for a human skeletal disorder.
              Article 0 comments Cited 164 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Bioengineered
                Journal ID (iso-abbrev): Bioengineered
                Title: Bioengineered
                Publisher: Taylor & Francis
                ISSN (Print): 2165-5979
                ISSN (Electronic): 2165-5987
                Publication date (Electronic, pub): 18 March 2021
                Publication date (Electronic, collection): 2021
                Publication date PMC-release: 18 March 2021
                Volume: 12
                Issue: 1
                Pages: 960-968
                Affiliations
                [a ]Department of Orthopedics, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College; , Hangzhou, Zhejiang, China
                [b ]Department of Orthopaedics, Dongyang Garden Tianshi Hospital; , Dongyang, Zhejiang, China
                Author notes
                CONTACT Fang Chai jkchai27@ 123456gmail.com Department of Orthopedics, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College; , No. 158 Shangtang Road, Hangzhou, Zhejiang 310014, China
                [*]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-3887-1525
                Article
                Publisher ID: 1900633
                DOI: 10.1080/21655979.2021.1900633
                PMC ID: 8291811
                PubMed ID: 33734011
                SO-VID: d86f278b-9f82-40c0-91aa-b8ab4718ebcd
                Copyright © © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 6, References: 40, Pages: 9
                Categories
                Subject: Research Article
                Subject: Research Paper

                ScienceOpen disciplines: Biomedical engineering
                Keywords: osteoporosis,trelagliptin,osteoblastic differentiation,runx2,ampk,mc3t3-e1
                Data availability:
                ScienceOpen disciplines: Biomedical engineering
                Keywords: osteoporosis, trelagliptin, osteoblastic differentiation, runx2, ampk, mc3t3-e1

                Comments

                Comment on this article

                scite_

                Similar content332

                See all similar

                Cited by13

                See all cited by

                Most referenced authors484

                See all reference authors