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PreprintCited 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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Chloé Yeung, Ching-Yan, 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.·2022·Matrix Biology
DOI 10.1101/2022.04.01.486699

Preprint — published as 10.1016/j.matbio.2023.10.002 · Paper page

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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: 83

  1. 10.1083/jcb.200312071 · DOI
  2. 10.7554/eLife.09345 · DOI
  3. 10.1016/S0092-8674(00)80064-1 · DOI · Paper page
  4. 10.1073/pnas.060037197 · DOI · Paper page
  5. 10.1038/s41556-019-0441-z · DOI
  6. 10.1038/370061a0 · DOI
  7. 10.1073/pnas.0305862101 · DOI · Paper page
  8. 10.1016/S0092-8674(03)00513-0 · DOI
  9. 10.1038/sj.bjc.6603863 · DOI
  10. 10.1074/jbc.M005631200 · DOI
  11. 10.1002/jcp.20065 · DOI
  12. Itoh, Y. Membrane-type matrix metalloproteinases: Their functions and regulations. Matrix Biol 44-46, 207–223 (2015). · DOI · Paper page
  13. 10.1074/jbc.M206874200 · DOI
  14. 10.1016/S0092-8674(00)81768-7 · DOI
  15. 10.1016/j.cell.2006.02.050 · DOI · Paper page
  16. 10.1101/gad.178749.111 · DOI
  17. 10.1083/jcb.200109100 · DOI · Paper page
  18. 10.1242/jcs.087858 · DOI
  19. 10.1038/nrm1766 · DOI
  20. 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. 10.1073/pnas.0906361106 · DOI · Paper page
  22. 10.1016/j.celrep.2012.07.005 · DOI
  23. 10.1126/science.1059542 · DOI
  24. 10.1073/pnas.0308709101 · DOI · Paper page
  25. 10.1038/nrg.2016.150 · DOI
  26. 10.1093/nar/gks1161 · DOI
  27. 10.1038/srep05183 · DOI
  28. 10.1016/j.jid.2016.03.036 · DOI
  29. 10.1038/nprot.2013.086 · DOI
  30. 2021, Age-related type I collagen modifications reveal tissue-defining differences between ligament and tendon, Matrix Biol Plus, 12, 100070, 10.1016/j.mbplus.2021.100070 · DOI
  31. 2007, Involvement of Pitx2, a homeodomain transcription factor, in hypothyroidism associated reproductive disorders, Cell Physiol Biochem, 20, 887, 10.1159/000110449 · DOI
  32. 10.1083/jcb.152.3.545 · DOI
  33. 10.1093/hmg/ddy074 · DOI
  34. 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. 10.1007/978-1-59745-413-1_9 · DOI
  36. 10.1083/jcb.130.1.227 · DOI
  37. 10.1073/pnas.87.15.5888 · DOI
  38. 10.1186/1471-2199-5-18 · DOI · Paper page
  39. 10.1038/ng1738 · DOI
  40. 10.1093/nar/gkx944 · DOI
  41. 2022, Circadian regulation of protein cargo in extracellular vesicles, Sci Adv, 8, eabc9061, 10.1126/sciadv.abc9061 · DOI
  42. 10.1038/nature11848 · DOI
  43. 10.1242/dev.001933 · DOI
  44. Kalson, N.S. et al. A structure-based extracellular matrix expansion mechanism of fibrous tissue growth. Elife 4 (2015). · DOI
  45. Gumucio, J.P. , Schonk, M.M. , Kharaz, Y.A. , Comerford, E. & Mendias, C.L. Scleraxis is required for the growth of adult tendons in response to mechanical loading. JCI Insight 5 (2020). · DOI
  46. 10.1152/ajpcell.00372.2020 · DOI
  47. 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. 10.1016/j.bbamcr.2017.05.013 · DOI
  49. 10.1002/(SICI)1097-0177(200004)217:4<430::AID-DVDY10>3.0.CO;2-5 · DOI
  50. 10.1074/jbc.M805582200 · DOI
  51. 10.1074/jbc.M110.102228 · DOI
  52. 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. 10.1074/jbc.M805721200 · DOI
  54. 10.1016/j.matbio.2010.01.001 · DOI
  55. 10.1111/febs.12235 · DOI
  56. 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
  57. 10.1074/jbc.RA119.010486 · DOI
  58. 2020, Membrane-type 1 Matrix Metalloproteinase Modulates Tissue Homeostasis by a Non-proteolytic Mechanism, iScience, 23, 101789, 10.1016/j.isci.2020.101789 · DOI
  59. Maybee, D.V. , Ink, N.L. & Ali, M.A.M. Novel Roles of MT1-MMP and MMP-2: Beyond the Extracellular Milieu. Int J Mol Sci 23 (2022). · DOI
  60. 10.1002/mc.20270 · DOI
  61. 10.1016/S0002-9440(10)61108-X · DOI
  62. 10.1016/j.ejcb.2012.05.003 · DOI · Paper page
  63. 10.1242/dev.093906 · DOI
  64. 10.1016/j.cell.2007.06.045 · DOI · Paper page
  65. 10.1126/science.8171325 · DOI · Paper page
  66. 10.1073/pnas.1400749111 · DOI
  67. 10.1371/journal.pone.0006529 · DOI
  68. Calverley, B.C. , Kadler, K.E. & Pickard, A. Dynamic High-Sensitivity Quantitation of Procollagen-I by Endogenous CRISPR-Cas9 NanoLuciferase Tagging. Cells 9 (2020). · DOI
  69. 2019, Preservation of circadian rhythms by the protein folding chaperone, BiP, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 7479, 10.1096/fj.201802366RR · DOI
  70. 2015, Chick tendon fibroblast transcriptome and shape depend on whether the cell has made its own collagen matrix, Scientific reports, 5, 13555, 10.1038/srep13555 · DOI
  71. 10.1006/meth.2001.1262 · DOI · Paper page
  72. 2020, BayesENproteomics: Bayesian Elastic Nets for Quantification of Peptidoforms in Complex Samples, J Proteome Res, 19, 2167, 10.1021/acs.jproteome.9b00468 · DOI
  73. 10.1038/s41467-019-11923-1 · DOI · Paper page
  74. 10.1038/nprot.2008.211 · DOI · Paper page
  75. 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
  76. 10.1074/mcp.M115.055897 · DOI · Paper page
  77. 10.1038/nprot.2016.136 · DOI
  78. 10.2202/1544-6115.1027 · DOI · Paper page
  79. 2015, Detecting Significant Changes in Protein Abundance, EuPA Open Proteom, 7, 11, 10.1016/j.euprot.2015.02.002 · DOI
  80. 10.1093/nar/gkz946 · DOI
  81. 10.1006/jsbi.1996.0013 · DOI
  82. 10.1038/nmeth.2089 · DOI · Paper page
  83. 10.1016/S0968-4328(00)00040-8 · DOI

Metadata

Authors
Chloé Yeung, C.-Y., 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
  • Manchester Academic Health Science Centre (GB)
  • University of Washington (US)
  • University of Oxford (GB)
  • University of Cologne (DE)
ORCID
Venue
Matrix Biology
Publisher
openRxiv
Published
2022-04-02
Volume
124
Pages
8-22
ISSN
0945-053X (ISSN-L)
DOI
10.1101/2022.04.01.486699
OpenAlex
W4388037287
Cited by
16
References
1
Citations by year
2026: 8 · 2025: 5 · 2024: 2 · 2022: 1
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
cc-by
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
  • Stowers Institute for Medical Research
  • Wellcome Trust (203128/Z/16/Z, 110126/Z/15/Z)
  • Shriners Hospitals for Children
  • University of Manchester (203128/Z/16/Z)
  • Deutsche Forschungsgemeinschaft (73111208‐SFB 829, SFB829, Project-ID 73111208-SFB829, 73111208, Project-ID 73111208)
  • Ministerstwo Edukacji i Nauki (1291/MOB/IV/2015/0)
  • Versus Arthritis (20875)
  • Sir Richard Stapley Educational Trust
  • National Institutes of Health (AR 037318)
  • Directorate for Biological Sciences
  • Medical Research Council (MR/T016744/1, MR/K019392/1, MR/P010709/1, 20875, MR/L011840/1, MR/T016744/1 and MR/P010709/1)
  • Biotechnology and Biological Sciences Research Council (BB/T001984/1, BB/L024551/1)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 037318)
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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