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Cited by 16Circadian rhythm and melatoninProtease and Inhibitor MechanismsTendon Structure and Treatment

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Mmp14 is required for matrisome homeostasis and circadian rhythm in fibroblasts

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Yeung, Ching-Yan Chloé, Garva, Richa, Pickard, Adam, Lu, Yinhui, Mallikarjun, Venkatesh, Swift, Joe, Taylor, Susan H., Rai, Jyoti, Eyre, David R., Chaturvedi, Mayank, Itoh, Yoshifumi, Meng, Qing-Jun, Mauch, Cornelia, Zigrino, Paola, Kadler, Karl E.·2023·Matrix Biology
DOI 10.1016/j.matbio.2023.10.002

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Abstract

The circadian clock in tendon regulates the daily rhythmic synthesis of collagen-I and the appearance and disappearance of small-diameter collagen fibrils in the extracellular matrix. How the fibrils are assembled and removed is not fully understood. Here, we first showed that the collagenase, membrane type I-matrix metalloproteinase (MT1-MMP, encoded by Mmp14), is regulated by the circadian clock in postnatal mouse tendon. Next, we generated tamoxifen-induced Col1a2-Cre-ERT2::Mmp14 KO mice (Mmp14 conditional knockout (CKO)). The CKO mice developed hind limb dorsiflexion and thickened tendons, which accumulated narrow-diameter collagen fibrils causing ultrastructural disorganization. Mass spectrometry of control tendons identified 1195 proteins of which 212 showed time-dependent abundance. In Mmp14 CKO mice 19 proteins had reversed temporal abundance and 176 proteins lost time dependency. Among these, the collagen crosslinking enzymes lysyl oxidase-like 1 (LOXL1) and lysyl hydroxylase 1 (LH1; encoded by Plod2) were elevated and had lost time-dependent regulation. High-pressure chromatography confirmed elevated levels of hydroxylysine aldehyde (pyridinoline) crosslinking of collagen in CKO tendons. As a result, collagen-I was refractory to extraction. We also showed that CRISPR-Cas9 deletion of Mmp14 from cultured fibroblasts resulted in loss of circadian clock rhythmicity of period 2 (PER2), and recombinant MT1-MMP was highly effective at cleaving soluble collagen-I but less effective at cleaving collagen pre-assembled into fibrils. In conclusion, our study shows that circadian clock-regulated Mmp14 controls the rhythmic synthesis of small diameter collagen fibrils, regulates collagen crosslinking, and its absence disrupts the circadian clock and matrisome in tendon fibroblasts.

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Research works printed but not linked: 85

  1. Canty, 2004, Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon, J. Cell Biol., 165, 553, 10.1083/jcb.200312071 · DOI
  2. Taylor, 2015, Matrix metalloproteinase 14 is required for fibrous tissue expansion, Elife, 4, e09345, 10.7554/eLife.09345 · DOI
  3. Holmbeck, 1999, MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover, Cell, 99, 81, 10.1016/S0092-8674(00)80064-1 · DOI · Paper page
  4. Zhou, 2000, Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I, Proc. Natl. Acad. Sci. USA, 97, 4052, 10.1073/pnas.060037197 · DOI · Paper page
  5. Chang, 2020, Circadian control of the secretory pathway maintains collagen homeostasis, Nat. Cell Biol., 22, 74, 10.1038/s41556-019-0441-z · DOI
  6. Sato, 1994, A matrix metalloproteinase expressed on the surface of invasive tumour cells, Nature, 370, 61, 10.1038/370061a0 · DOI
  7. Tam, 2004, Membrane protease proteomics: isotope-coded affinity tag MS identification of undescribed MT1-matrix metalloproteinase substrates, Proc. Natl. Acad. Sci. USA, 101, 6917, 10.1073/pnas.0305862101 · DOI · Paper page
  8. Hotary, 2003, Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix, Cell, 114, 33, 10.1016/S0092-8674(03)00513-0 · DOI
  9. Sodek, 2007, MT1-MMP is the critical determinant of matrix degradation and invasion by ovarian cancer cells, Br. J. Cancer, 97, 358, 10.1038/sj.bjc.6603863 · DOI
  10. Ellerbroek, 2001, Functional interplay between type I collagen and cell surface matrix metalloproteinase activity, J. Biol. Chem., 276, 24833, 10.1074/jbc.M005631200 · DOI
  11. Holmbeck, 2004, MT1-MMP: a tethered collagenase, J. Cell Physiol., 200, 11, 10.1002/jcp.20065 · DOI
  12. Itoh, 2015, Membrane-type matrix metalloproteinases: their functions and regulations, Matrix Biol., 44–46, 207, 10.1016/j.matbio.2015.03.004 · DOI · Paper page
  13. Tam, 2002, Collagen binding properties of the membrane type-1 matrix metalloproteinase (MT1-MMP) hemopexin C domain. The ectodomain of the 44-kDa autocatalytic product of MT1-MMP inhibits cell invasion by disrupting native type I collagen cleavage, J. Biol. Chem., 277, 39005, 10.1074/jbc.M206874200 · DOI
  14. Hiraoka, 1998, Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins, Cell, 95, 365, 10.1016/S0092-8674(00)81768-7 · DOI
  15. Chun, 2006, A pericellular collagenase directs the 3-dimensional development of white adipose tissue, Cell, 125, 577, 10.1016/j.cell.2006.02.050 · DOI · Paper page
  16. Shimizu-Hirota, 2012, MT1-MMP regulates the PI3Kdelta.Mi-2/NuRD-dependent control of macrophage immune function, Genes Dev., 26, 395, 10.1101/gad.178749.111 · DOI
  17. Mu, 2002, The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1, J. Cell Biol., 157, 493, 10.1083/jcb.200109100 · DOI · Paper page
  18. Shi, 2011, MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin, J. Cell Sci., 124, 4039, 10.1242/jcs.087858 · DOI
  19. Roenneberg, 2005, Circadian clocks - the fall and rise of physiology, Nat. Rev. Mol. Cell Biol., 6, 965, 10.1038/nrm1766 · DOI
  20. Aggarwal, 2017, The Circadian clock regulates adipogenesis by a Per3 crosstalk pathway to Klf15, Cell Rep., 21, 2367, 10.1016/j.celrep.2017.11.004 · DOI
  21. Jensen, 2012, Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish, Cell Rep., 2, 231, 10.1016/j.celrep.2012.07.005 · DOI
  22. Yagita, 2001, Molecular mechanisms of the biological clock in cultured fibroblasts, Science, 292, 278, 10.1126/science.1059542 · DOI
  23. Yoo, 2004, PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues, Proc. Natl. Acad. Sci. USA, 101, 5339, 10.1073/pnas.0308709101 · DOI · Paper page
  24. Takahashi, 2017, Transcriptional architecture of the mammalian circadian clock, Nat. Rev. Genet., 18, 164, 10.1038/nrg.2016.150 · DOI
  25. Pizarro, 2013, CircaDB: a database of mammalian circadian gene expression profiles, Nucl. Acids Res., 41, D1009, 10.1093/nar/gks1161 · DOI
  26. Yeung, 2014, Gremlin-2 is a BMP antagonist that is regulated by the circadian clock, Sci. Rep., 4, 5183, 10.1038/srep05183 · DOI
  27. Zigrino, 2016, Fibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin, J. Invest. Dermatol., 136, 1575, 10.1016/j.jid.2016.03.036 · DOI
  28. Starborg, 2013, Using transmission electron microscopy and 3View to determine collagen fibril size and three-dimensional organization, Nat. Protoc., 8, 1433, 10.1038/nprot.2013.086 · DOI
  29. Shao, 2020, MatrisomeDB: the ECM-protein knowledge database, Nucl. Acids Res., 48, D1136, 10.1093/nar/gkz849 · DOI
  30. Hudson, 2021, Age-related type I collagen modifications reveal tissue-defining differences between ligament and tendon, Matrix Biol. Plus, 12, 10.1016/j.mbplus.2021.100070 · DOI
  31. Ghosh, 2007, Involvement of Pitx2, a homeodomain transcription factor, in hypothyroidism associated reproductive disorders, Cell Physiol. Biochem., 20, 887, 10.1159/000110449 · DOI
  32. Hjalt, 2001, PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: implications for the pathology of Rieger syndrome, J. Cell Biol., 152, 545, 10.1083/jcb.152.3.545 · DOI
  33. Hendee, 2018, PITX2 deficiency and associated human disease: insights from the zebrafish model, Hum. Mol. Genet., 27, 1675, 10.1093/hmg/ddy074 · DOI
  34. Itoh, 2021, A common SNP risk variant MT1-MMP causative for Dupuytren's disease has a specific defect in collagenolytic activity, Matrix Biol., 97, 20, 10.1016/j.matbio.2021.02.003 · DOI
  35. Sherratt, 2009, Mass-mapping of ECM macromolecules by scanning transmission electron microscopy, Methods Mol. Biol., 522, 151, 10.1007/978-1-59745-413-1_9 · DOI
  36. Perumal, 2008, Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis, Proc. Natl. Acad. Sci. USA, 105, 2824, 10.1073/pnas.0710588105 · DOI
  37. Liu, 1995, A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling, J. Cell Biol., 130, 227, 10.1083/jcb.130.1.227 · DOI
  38. Wu, 1990, Generation of collagenase-resistant collagen by site-directed mutagenesis of murine pro alpha 1(I) collagen gene, Proc. Natl. Acad. Sci. USA, 87, 5888, 10.1073/pnas.87.15.5888 · DOI
  39. Ripperger, 2006, Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions, Nat. Genet., 38, 369, 10.1038/ng1738 · DOI
  40. Li, 2018, CirGRDB: a database for the genome-wide deciphering circadian genes and regulators, Nucl. Acids Res., 46, D64, 10.1093/nar/gkx944 · DOI
  41. Yeung, 2022, Circadian regulation of protein cargo in extracellular vesicles, Sci. Adv., 8, eabc9061, 10.1126/sciadv.abc9061 · DOI
  42. Schwanhausser, 2013, Corrigendum: global quantification of mammalian gene expression control, Nature, 495, 126, 10.1038/nature11848 · DOI
  43. Murchison, 2007, Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons, Development, 134, 2697, 10.1242/dev.001933 · DOI
  44. Kalson, 2015, A structure-based extracellular matrix expansion mechanism of fibrous tissue growth, Elife, 4, 10.7554/eLife.05958 · DOI
  45. Gumucio, 2020, Scleraxis is required for the growth of adult tendons in response to mechanical loading, JCI Insight, 5, 10.1172/jci.insight.138295 · DOI
  46. De Micheli, 2020, Single-cell transcriptomic analysis identifies extensive heterogeneity in the cellular composition of mouse Achilles tendons, Am. J. Physiol. Cell Physiol., 319, C885, 10.1152/ajpcell.00372.2020 · DOI
  47. Varcoe, 2018, Maternal circadian rhythms and the programming of adult health and disease, Am. J. Physiol. Regul. Integr. Comp. Physiol., 314, R231, 10.1152/ajpregu.00248.2017 · DOI
  48. Jobin, 2017, New intracellular activities of matrix metalloproteinases shine in the moonlight, Biochim. Biophys. Acta Mol. Cell Res., 1864, 2043, 10.1016/j.bbamcr.2017.05.013 · DOI
  49. Young, 2000, Expression of type XIV collagen in developing chicken tendons: association with assembly and growth of collagen fibrils, Dev. Dyn., 217, 430, 10.1002/(SICI)1097-0177(200004)217:4<430::AID-DVDY10>3.0.CO;2-5 · DOI
  50. Ansorge, 2009, Type Xiv collagen regulates fibrillogenesis: premature collagen fibril growth and tissue dysfunction in null mice, J. Biol. Chem., 284, 8427, 10.1074/jbc.M805582200 · DOI
  51. Vranka, 2010, Prolyl 3-hydroxylase 1 null mice display abnormalities in fibrillar collagen-rich tissues such as tendons, skin, and bones, J. Biol. Chem., 285, 17253, 10.1074/jbc.M110.102228 · DOI
  52. Chin, 1985, Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by stimulated rabbit synovial fibroblasts in parallel with collagenase. Biosynthesis, isolation, characterization, and substrates, J. Biol. Chem., 260, 12367, 10.1016/S0021-9258(17)39034-8 · DOI
  53. Kalamajski, 2010, The role of small leucine-rich proteoglycans in collagen fibrillogenesis, Matrix Biol., 29, 248, 10.1016/j.matbio.2010.01.001 · DOI
  54. Kalamajski, 2009, Homologous sequence in lumican and fibromodulin leucine-rich repeat 5-7 competes for collagen binding, J. Biol. Chem., 284, 534, 10.1074/jbc.M805721200 · DOI
  55. Mohammadzadeh, 2019, The extracellular matrix proteoglycan lumican improves survival and counteracts cardiac dilatation and failure in mice subjected to pressure overload, Sci. Rep., 9, 9206, 10.1038/s41598-019-45651-9 · DOI
  56. Jobin, 2020, Moonlighting matrix metalloproteinase substrates: enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage, J. Biol. Chem., 295, 2186, 10.1074/jbc.RA119.010486 · DOI
  57. Attur, 2020, Membrane-type 1 matrix metalloproteinase modulates tissue homeostasis by a non-proteolytic mechanism, iScience, 23, 101789, 10.1016/j.isci.2020.101789 · DOI
  58. Maybee, 2022, Novel roles of MT1-MMP and MMP-2: beyond the extracellular milieu, Int. J. Mol. Sci., 23, 10.3390/ijms23179513 · DOI
  59. Ip, 2007, Atypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma, Mol. Carcinog., 46, 225, 10.1002/mc.20270 · DOI
  60. Yang, 2017, Cellular mechano-environment regulates the mammary circadian clock, Nat. Commun., 8, 14287, 10.1038/ncomms14287 · DOI
  61. Zheng, 2002, Ligand-dependent genetic recombination in fibroblasts : a potentially powerful technique for investigating gene function in fibrosis, Am. J. Pathol., 160, 1609, 10.1016/S0002-9440(10)61108-X · DOI
  62. Zigrino, 2012, Loss of epidermal MMP-14 expression interferes with angiogenesis but not with re-epithelialization, Eur. J. Cell Biol., 91, 748, 10.1016/j.ejcb.2012.05.003 · DOI · Paper page
  63. Blitz, 2013, Tendon-bone attachment unit is formed modularly by a distinct pool of Scx- and Sox9-positive progenitors, Development, 140, 2680, 10.1242/dev.093906 · DOI
  64. Storch, 2007, Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information, Cell, 130, 730, 10.1016/j.cell.2007.06.045 · DOI · Paper page
  65. Rosse, 2014, Control of MT1-MMP transport by atypical PKC during breast-cancer progression, Proc. Natl. Acad. Sci. USA, 111, E1872, 10.1073/pnas.1400749111 · DOI
  66. Campeau, 2009, A versatile viral system for expression and depletion of proteins in mammalian cells, PLoS One, 4, e6529, 10.1371/journal.pone.0006529 · DOI
  67. Calverley, 2020, Dynamic high-sensitivity quantitation of procollagen-I by endogenous CRISPR-Cas9 NanoLuciferase tagging, Cells, 9, 2070, 10.3390/cells9092070 · DOI
  68. Pickard, 2019, Preservation of circadian rhythms by the protein folding chaperone, BiP, FASEB J., 33, 7479, 10.1096/fj.201802366RR · DOI
  69. Yeung, 2015, Chick tendon fibroblast transcriptome and shape depend on whether the cell has made its own collagen matrix, Sci. Rep., 5, 13555, 10.1038/srep13555 · DOI
  70. Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262 · DOI · Paper page
  71. Mallikarjun, 2020, BayesENproteomics: Bayesian elastic nets for quantification of peptidoforms in complex samples, J. Proteome Res., 19, 2167, 10.1021/acs.jproteome.9b00468 · DOI
  72. Gilbert, 2019, Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading, Nat. Commun., 10, 4149, 10.1038/s41467-019-11923-1 · DOI · Paper page
  73. Huang da, 2009, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat. Protoc., 4, 44, 10.1038/nprot.2008.211 · DOI · Paper page
  74. Bekker-Jensen, 2017, An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes, Cell Syst, 4, 587, 10.1016/j.cels.2017.05.009 · DOI
  75. Goeminne, 2016, Peptide-level robust ridge regression improves estimation, sensitivity, and specificity in data-dependent quantitative label-free shotgun proteomics, Mol. Cell Proteom., 15, 657, 10.1074/mcp.M115.055897 · DOI · Paper page
  76. Tyanova, 2016, The MaxQuant computational platform for mass spectrometry-based shotgun proteomics, Nat. Protoc., 11, 2301, 10.1038/nprot.2016.136 · DOI
  77. Huber, 1964, Robust estimation of a location parameter, Ann. Math. Stat., 35, 73, 10.1214/aoms/1177703732 · DOI · Paper page
  78. Smyth, 2004, Linear models and empirical Bayes methods for assessing differential expression in microarray experiments, Stat. Appl. Genet. Mol. Biol., 3, 10.2202/1544-6115.1027 · DOI · Paper page
  79. Kammers, 2015, Detecting significant changes in protein abundance, EuPA Open Proteom., 7, 11, 10.1016/j.euprot.2015.02.002 · DOI
  80. Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. R. Stat. Soc., 57, 289, 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page
  81. Rodchenkov, 2020, Pathway commons 2019 update: integration, analysis and exploration of pathway data, Nucl. Acids Res., 48, D489
  82. Creemers, 1997, Microassay for the assessment of low levels of hydroxyproline, BioTechniques, 22, 656, 10.2144/97224bm19 · DOI
  83. Kremer, 1996, Computer visualization of three-dimensional image data using IMOD, J. Struct. Biol., 116, 71, 10.1006/jsbi.1996.0013 · DOI
  84. Schneider, 2012, NIH image to ImageJ: 25 years of image analysis, Nat. Methods, 9, 671, 10.1038/nmeth.2089 · DOI · Paper page
  85. Holmes, 2001, STEM/TEM studies of collagen fibril assembly, Micron, 32, 273, 10.1016/S0968-4328(00)00040-8 · DOI

Metadata

Authors
Yeung, C.-Y. C., Garva, R., Pickard, A., Lu, Y., Mallikarjun, V., Swift, J., Taylor, S. H., Rai, J., Eyre, D. R., Chaturvedi, M., Itoh, Y., Meng, Q.-J., Mauch, C., Zigrino, P., & Kadler, K. E.
Affiliations
  • University of Copenhagen (DK)
  • Manchester Academic Health Science Centre (GB)
  • University of Washington (US)
  • University of Oxford (GB)
  • University of Cologne (DE)
Corresponding author
Yeung, Ching-Yan Chloé
ORCID
Venue
Matrix Biology
Publisher
Elsevier BV
Published
2023-12
Volume
124
Pages
8-22
ISSN
0945-053X (ISSN-L)
DOI
10.1016/j.matbio.2023.10.002
OpenAlex
W4388037287
Cited by
16
References
4
Citations by year
2026: 8 · 2025: 5 · 2024: 2
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Matrix Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • Research Explorer (The University of Manchester) (submittedVersion, cc-by)
Funders
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR037318)
  • BBSRC (BB/L024551/1, BB/T001984/1)
  • Deutsche Forschungsgemeinschaft (Project-ID 73111208-SFB829, SFB 829, 73111208-SFB829)
  • NIH
  • Versus Arthritis
  • Stowers Institute for Medical Research
  • Shriners Hospitals for Children
  • Wellcome Trust (110126/Z/15/Z, 203128/Z/16/Z)
  • The Sir Richard Stapley Educational Trust
  • Polish Ministry of Science and Higher Education (1291/MOB/IV/2015/0)
  • University of Manchester
  • Medical Research Council (MR/T016744/1, 20875, MR/P010709/1)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
Keywords
MMP-14, MT1-MMP, circadian clock, matrisome, tendons, type I collagen, collagen fibril assembly, collagen cross-linking, pyridinoline, Per2, tendon fibroblasts, LOXL1, collagenase, tendon thickening
MeSH terms
Animals, Circadian Rhythm, Collagen, Extracellular Matrix, Fibroblasts, Homeostasis, Mice, Matrix Metalloproteinase 14

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