Home LiteratureArticle Details
PMID: 12972593 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of metalloprotease disintegrin ADAM12 in determination of quiescent reserve cells during myogenic differentiation in vitro.

Molecular and cellular biology ·Vol. 23 ·No. 19 ·2003-10-00 ·Pages 6725-38

Cao Y, Zhao Z, Gruszczynska-Biegala J, Zolkiewska A

Abstract

Skeletal myoblasts grown in vitro and induced to differentiate either form differentiated multinucleated myotubes or give rise to quiescent, undifferentiated "reserve cells" that share several characteristics with muscle satellite cells. The mechanism of determination of reserve cells is poorly understood. We find that the expression level of the metalloprotease disintegrin ADAM12 is much higher in proliferating C2C12 myoblasts and in reserve cells than in myotubes. Inhibition of ADAM12 expression in differentiating C2C12 cultures by small interfering RNA is accompanied by lower expression levels of both quiescence markers (retinoblastoma-related protein p130 and cell cycle inhibitor p27) and differentiation markers (myogenin and integrin alpha7A isoform). Overexpression of ADAM12 in C2C12 cells under conditions that promote cell cycle progression leads to upregulation of p130 and p27, cell cycle arrest, and downregulation of MyoD. Thus, enhanced expression of ADAM12 induces a quiescence-like phenotype and does not stimulate differentiation. We also show that the region extending from the disintegrin to the transmembrane domain of ADAM12 and containing cell adhesion activity as well as the cytoplasmic domain of ADAM12 are required for ADAM12-mediated cell cycle arrest, while the metalloprotease domain is not essential. Our results suggest that ADAM12-mediated adhesion and/or signaling may play a role in determination of the pool of reserve cells during myoblast differentiation.

MeSH Terms
ADAM Proteins ADAM12 Protein Animals Biomarkers Carrier Proteins/metabolism Cell Cycle Cell Differentiation/physiology Cell Division Cell Line Disintegrins/metabolism Gene Expression Regulation Integrin alpha Chains/metabolism Membrane Proteins/chemistry,genetics,physiology Metalloendopeptidases/metabolism Mice Muscle Fibers, Skeletal/physiology Muscle Proteins/chemistry,genetics,physiology Muscle, Skeletal/embryology Mutation MyoD Protein/metabolism Myogenin/metabolism Protein Structure, Tertiary RNA, Small Interfering/metabolism Retinoblastoma-Binding Protein 1
Chemicals
Arid4a protein, mouse Biomarkers Carrier Proteins Disintegrins Integrin alpha Chains Membrane Proteins Muscle Proteins MyoD Protein Myog protein, mouse Myogenin RNA, Small Interfering Retinoblastoma-Binding Protein 1 ADAM Proteins ADAM12 Protein Adam12 protein, mouse Metalloendopeptidases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cao Yi
Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA.
Zhao Zhefeng
Gruszczynska-Biegala Joanna
Zolkiewska Anna
References (68)
68 references, click to expand
  1. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD.
    Science. 1995 Feb 17;267(5200):1018-21 PMID: 7863327
  2. Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase.
    Science. 1995 Feb 17;267(5200):1022-4 PMID: 7863328
  3. p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells.
    Science. 1995 Feb 17;267(5200):1024-7 PMID: 7863329
  4. A metalloprotease-disintegrin participating in myoblast fusion.
    Nature. 1995 Oct 19;377(6550):652-6 PMID: 7566181
  5. Macrocyclic hydroxamate inhibitors of matrix metalloproteinases and TNF-alpha production.
    Bioorg Med Chem Lett. 1999 May 3;9(9):1279-84 PMID: 10340614
  6. The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD.
    Dev Biol. 1999 Jun 15;210(2):440-55 PMID: 10357902
  7. Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review).
    J Protein Chem. 1999 May;18(4):447-65 PMID: 10449042
  8. Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding.
    J Cell Sci. 1999 Nov;112 ( Pt 21):3603-17 PMID: 10523497
  9. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy.
    Nat Med. 2002 Jan;8(1):35-40 PMID: 11786904
  10. Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors.
    Mol Cell Biol. 2002 Apr;22(7):2025-36 PMID: 11884591
  11. ADAM 12 protease induces adipogenesis in transgenic mice.
    Am J Pathol. 2002 May;160(5):1895-903 PMID: 12000741
  12. Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions.
    J Biol Chem. 2002 May 17;277(20):17804-10 PMID: 11882657
  13. Paradigms of growth control: relation to Cdk activation.
    Sci STKE. 2002 May 28;2002(134):re7 PMID: 12034920
  14. Intracellular processing of metalloprotease disintegrin ADAM12.
    J Biol Chem. 2002 Jul 19;277(29):26403-11 PMID: 12000744
  15. p27Kip1: a key regulator of skeletal muscle satellite cell proliferation.
    Clin Orthop Relat Res. 2002 Oct;(403 Suppl):S221-7 PMID: 12394472
  16. ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice.
    Am J Pathol. 2002 Nov;161(5):1535-40 PMID: 12414501
  17. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression.
    J Biol Chem. 2002 Dec 20;277(51):49831-40 PMID: 12244043
  18. Phenotypic analysis of Meltrin alpha (ADAM12)-deficient mice: involvement of Meltrin alpha in adipogenesis and myogenesis.
    Mol Cell Biol. 2003 Jan;23(1):55-61 PMID: 12482960
  19. Muscle regeneration: molecular aspects and therapeutic implications.
    Curr Opin Neurol. 1999 Oct;12(5):535-43 PMID: 10590890
  20. MyoD is required for myogenic stem cell function in adult skeletal muscle.
    Genes Dev. 1996 May 15;10(10):1173-83 PMID: 8675005
  21. Resistance to apoptosis conferred by Cdk inhibitors during myocyte differentiation.
    Science. 1996 Jul 19;273(5273):359-61 PMID: 8662523
  22. Defining the regulatory networks for muscle development.
    Curr Opin Genet Dev. 1996 Aug;6(4):445-53 PMID: 8791524
  23. Induction of p18INK4c and its predominant association with CDK4 and CDK6 during myogenic differentiation.
    Mol Biol Cell. 1996 Oct;7(10):1587-99 PMID: 8898364
  24. Skeletal muscle determination and differentiation: story of a core regulatory network and its context.
    Curr Opin Cell Biol. 1996 Dec;8(6):877-89 PMID: 8939680
  25. The accumulation of an E2F-p130 transcriptional repressor distinguishes a G0 cell state from a G1 cell state.
    Mol Cell Biol. 1996 Dec;16(12):6965-76 PMID: 8943352
  26. Inhibition of fibrillin 1 expression using U1 snRNA as a vehicle for the presentation of antisense targeting sequence.
    Hum Mol Genet. 1997 Apr;6(4):519-25 PMID: 9097954
  27. Cell cycle exit upon myogenic differentiation.
    Curr Opin Genet Dev. 1997 Oct;7(5):597-602 PMID: 9388774
  28. Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells.
    Dev Biol. 1997 Nov 15;191(2):270-83 PMID: 9398440
  29. A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo.
    J Biol Chem. 1998 Jan 2;273(1):157-66 PMID: 9417060
  30. Cell cycle-regulated expression of the muscle determination factor Myf5 in proliferating myoblasts.
    J Cell Biol. 1998 Jan 12;140(1):111-8 PMID: 9425159
  31. p27Kip1 is expressed transiently in developing myotomes and enhances myogenesis.
    Cell Growth Differ. 1998 Jan;9(1):1-11 PMID: 9438383
  32. Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates 'reserve cells'.
    J Cell Sci. 1998 Mar;111 ( Pt 6):769-79 PMID: 9472005
  33. Human ADAM 12 (meltrin alpha) is an active metalloprotease.
    J Biol Chem. 1998 Jul 3;273(27):16993-7 PMID: 9642263
  34. The muscle regulatory factors MyoD and myf-5 undergo distinct cell cycle-specific expression in muscle cells.
    J Cell Biol. 1998 Sep 21;142(6):1447-59 PMID: 9744876
  35. Muscle differentiation: more complexity to the network of myogenic regulators.
    Curr Opin Genet Dev. 1998 Oct;8(5):539-44 PMID: 9794824
  36. ADAMs: focus on the protease domain.
    Curr Opin Cell Biol. 1998 Oct;10(5):654-9 PMID: 9818177
  37. Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle.
    J Cell Biol. 1999 Feb 22;144(4):631-43 PMID: 10037786
  38. Maturation of the myogenic program is induced by postmitotic expression of insulin-like growth factor I.
    Mol Cell Biol. 1999 Apr;19(4):3115-24 PMID: 10082578
  39. The alpha7beta1 integrin in muscle development and disease.
    Cell Tissue Res. 1999 Apr;296(1):183-90 PMID: 10199978
  40. Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion.
    Am J Pathol. 1999 May;154(5):1489-501 PMID: 10329602
  41. A new look at the origin, function, and "stem-cell" status of muscle satellite cells.
    Dev Biol. 2000 Feb 15;218(2):115-24 PMID: 10656756
  42. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1.
    Nature. 2000 Apr 13;404(6779):782-7 PMID: 10783894
  43. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion.
    J Biol Chem. 2000 May 5;275(18):13933-9 PMID: 10788519
  44. The retinoblastoma-like protein p130 is involved in the determination of reserve cells in differentiating myoblasts.
    Curr Biol. 2000 May 4;10(9):543-6 PMID: 10801445
  45. The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading.
    J Cell Biol. 2000 May 29;149(5):1143-56 PMID: 10831617
  46. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3.
    J Biol Chem. 2000 Jun 16;275(24):18574-80 PMID: 10849447
  47. Involvement of p27(kip1) and cyclin D3 in the regulation of cdk2 activity during skeletal muscle differentiation.
    Biochim Biophys Acta. 2000 Jul 21;1497(2):175-85 PMID: 10903422
  48. Trafficking of human ADAM 12-L: retention in the trans-Golgi network.
    Biochem Biophys Res Commun. 2000 Aug 28;275(2):261-7 PMID: 10964655
  49. Molecular mechanisms regulating myogenic determination and differentiation.
    Front Biosci. 2000 Sep 1;5:D750-67 PMID: 10966875
  50. RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.
    J Biol Chem. 2000 Nov 10;275(45):34922-30 PMID: 10944520
  51. ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3.
    Biochem Biophys Res Commun. 2000 Nov 30;278(3):511-5 PMID: 11095942
  52. Metalloprotease-disintegrin ADAM 12 binds to the SH3 domain of Src and activates Src tyrosine kinase in C2C12 cells.
    Biochem J. 2000 Dec 15;352 Pt 3:883-92 PMID: 11104699
  53. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation.
    J Biol Chem. 2000 Dec 22;275(51):40235-43 PMID: 10976104
  54. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells.
    J Cell Biol. 2000 Dec 11;151(6):1221-34 PMID: 11121437
  55. Analysis for transcript expression of meltrin alpha in normal, regenerating, and denervated rat muscle.
    J Muscle Res Cell Motil. 2000;21(5):475-80 PMID: 11129438
  56. A calcineurin- and NFAT-dependent pathway regulates Myf5 gene expression in skeletal muscle reserve cells.
    J Cell Sci. 2001 Jan;114(Pt 2):303-10 PMID: 11148132
  57. Crosstalk between cell cycle regulators and the myogenic factor MyoD in skeletal myoblasts.
    Cell Mol Life Sci. 2001 Apr;58(4):571-9 PMID: 11361092
  58. Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells.
    J Biol Chem. 2001 Jul 6;276(27):24466-72 PMID: 11313349
  59. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice.
    Mech Ageing Dev. 2001 Sep;122(12):1303-20 PMID: 11438121
  60. Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation.
    Mol Cell Biol. 2001 Aug;21(15):4960-7 PMID: 11438653
  61. Metalloprotease-disintegrin ADAM 12 interacts with alpha-actinin-1.
    Biochem J. 2001 Jul 15;357(Pt 2):353-61 PMID: 11439084
  62. Myogenic satellite cells: physiology to molecular biology.
    J Appl Physiol (1985). 2001 Aug;91(2):534-51 PMID: 11457764
  63. Regulation of myostatin activity and muscle growth.
    Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9306-11 PMID: 11459935
  64. Skeletal muscle cell hypertrophy induced by inhibitors of metalloproteases; myostatin as a potential mediator.
    Am J Physiol Cell Physiol. 2001 Nov;281(5):C1624-34 PMID: 11600426
  65. The p130 pocket protein: keeping order at cell cycle exit/re-entrance transitions.
    Front Biosci. 1998;3:d11-24 PMID: 9405335
  66. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development.
    Cell. 1992 Oct 30;71(3):383-90 PMID: 1330322
  67. Skeletal muscle satellite cells.
    Rev Physiol Biochem Pharmacol. 1994;123:213-57 PMID: 8209136
  68. Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers.
    Dev Biol. 1994 Aug;164(2):588-603 PMID: 7913900
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.19.6725-6738.2003
Published
2003-10-00
Pages
6725-38
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC193919
Subset
IM
Grants
NCRR NIH HHS · P20 RR017708 · United States
External Links
PubMed source DOI: 10.1128/MCB.23.19.6725-6738.2003 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2