{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:15:11Z","timestamp":1790673311449,"version":"4.1.0"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23659727"],"award-info":[{"award-number":["23659727"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019323","name":"Institute for Enzyme Research, University of Tokushima","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100019323","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Connective tissues such as tendon, ligament and cartilage are mostly composed of extracellular matrix (ECM). These tissues are insoluble, mainly due to the highly cross-linked ECM proteins such as collagens. Difficulties obtaining suitable samples for mass spectrometric analysis render the application of modern proteomic technologies difficult. Complete solubilization of them would not only elucidate protein composition of normal tissues but also reveal pathophysiology of pathological tissues. Here we report complete solubilization of human Achilles tendon and yellow ligament, which is achieved by chemical digestion combined with successive protease treatment including elastase. The digestion mixture was subjected to liquid chromatography\u2013mass spectrometry. The low specificity of elastase was overcome by accurate mass analysis achieved using FT-ICR-MS. In addition to the detailed proteome of both tissues, we also quantitatively determine the major protein composition of samples, by measuring peak area of some characteristic peptides detected in tissue samples and in purified proteins. As a result, differences between human Achilles tendon and yellow ligament were elucidated at molecular level.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6b00806","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T08:23:27Z","timestamp":1476692607000},"page":"4709-4721","source":"Crossref","is-referenced-by-count":40,"title":["Proteomic Analysis\nof Human Tendon and Ligament: Solubilization\nand Analysis of Insoluble Extracellular Matrix in Connective Tissues"],"prefix":"10.1021","volume":"15","author":[{"given":"Nori","family":"Sato","sequence":"first","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Tokushima University , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Goda","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Higashino","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Sakai","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Katoh","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuo","family":"Yasui","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Sairyo","sequence":"additional","affiliation":[{"name":"Tokushima University Graduate School , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisaaki","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Tokushima University , , 3-18-15 Kuramoto-cho , ,","place":["Tokushima, Japan, 770-8503"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,10,17]]},"reference":[{"key":"2026081810434535500_cit1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/jor.1100010305","article-title":"Tendons and\nligaments: a morphological and biochemical comparison","volume":"1","author":"Amiel","year":"1984","journal-title":"J. Orthop. Res."},{"key":"2026081810434535500_cit2","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1017\/erm.2013.9","article-title":"Elastic\nfibres in health and disease","volume":"15","author":"Baldwin","year":"2013","journal-title":"Expert Rev. Mol.\nMed."},{"key":"2026081810434535500_cit3","first-page":"213","article-title":"Form and Function\nof Tendon and Ligament","volume-title":"Orthopaedic Basic\nScience: Foundations of Clinical Practice","author":"Reuther","year":"2013","edition":"4"},{"key":"2026081810434535500_cit4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/1523-1747.ep12530093","article-title":"Biochemistry\nof the elastic fibers in normal connective tissues and its alterations\nin diseases","volume":"72","author":"Uitto","year":"1979","journal-title":"J. Invest. Dermatol."},{"key":"2026081810434535500_cit5","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nature13302","article-title":"A draft map of the human proteome","volume":"509","author":"Kim","year":"2014","journal-title":"Nature"},{"key":"2026081810434535500_cit6","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nature13319","article-title":"Mass-spectrometry-based\ndraft of the human proteome","volume":"509","author":"Wilhelm","year":"2014","journal-title":"Nature"},{"key":"2026081810434535500_cit7","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1034\/j.1600-0838.2000.010006312.x","article-title":"Structure\nof the tendon connective tissue","volume":"10","author":"Kannus","year":"2000","journal-title":"Scandinavian\njournal of medicine & science in sports"},{"key":"2026081810434535500_cit8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/B978-0-12-775170-2.50014-7","article-title":"Elastic fiber\nstructure and assembly","volume-title":"Extracellular Matrix\nAssembly and Structure","author":"Mecham","year":"1994"},{"key":"2026081810434535500_cit9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/0076-6879(87)44178-5","article-title":"Elastin: an\noverview","volume":"144","author":"Rosenbloom","year":"1987","journal-title":"Methods Enzymol."},{"key":"2026081810434535500_cit10","first-page":"188","article-title":"Biomechanical\nstudy of human lumbar ligamentum flavum","volume":"105","author":"Evans","year":"1969","journal-title":"J.\nAnat."},{"key":"2026081810434535500_cit11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/wdev.201","article-title":"Tendon development\nand diseases","volume":"5","author":"Gaut","year":"2016","journal-title":"Wiley Interdiscip Rev. 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Eng."},{"key":"2026081810434535500_cit15","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1002\/jor.22818","article-title":"Tendon\nfunctional extracellular matrix","volume":"33","author":"Screen","year":"2015","journal-title":"J. Orthop.\nRes."},{"key":"2026081810434535500_cit16","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/BF00449940","article-title":"Elastin in the human\nintervertebral disk. A histological and biochemical study comparing\nit with elastin in the human yellow ligament","volume":"105","author":"Mikawa","year":"1986","journal-title":"Archives of orthopaedic and traumatic surgery. Archiv fur orthopadische\nund Unfall-Chirurgie"},{"key":"2026081810434535500_cit17","doi-asserted-by":"publisher","first-page":"3969","DOI":"10.1016\/j.febslet.2010.07.055","article-title":"Induction of endosomal\/lysosomal pathways in differentiating\nosteoblasts as revealed by combined proteomic and transcriptomic analyses","volume":"584","author":"Taniguchi","year":"2010","journal-title":"FEBS Lett."},{"key":"2026081810434535500_cit18","doi-asserted-by":"publisher","first-page":"14628","DOI":"10.1073\/pnas.1306939110","article-title":"Human alpha-L-iduronidase uses its\nown N-glycan as a substrate-binding and catalytic module","volume":"110","author":"Maita","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081810434535500_cit19","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1074\/jbc.M305623200","article-title":"Proteomic\nanalysis of rat liver peroxisome:\npresence of peroxisome-specific isozyme of Lon protease","volume":"279","author":"Kikuchi","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2026081810434535500_cit20","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/85686","article-title":"Large-scale analysis\nof the yeast proteome by multidimensional protein identification technology","volume":"19","author":"Washburn","year":"2001","journal-title":"Nat. Biotechnol."},{"key":"2026081810434535500_cit21","doi-asserted-by":"crossref","first-page":"12084","DOI":"10.1016\/S0021-9258(19)86432-3","article-title":"The isolation and characterization of the cyanogen\nbromide peptides from the B chain of human collagen","volume":"254","author":"Rhodes","year":"1979","journal-title":"J. Biol. 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Biochem."},{"key":"2026081810434535500_cit23","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1002\/prot.20643","article-title":"Characterization of peptides resulting\nfrom digestion of human skin elastin with elastase","volume":"61","author":"Getie","year":"2005","journal-title":"Proteins: Struct., Funct., Genet."},{"key":"2026081810434535500_cit24","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.matbio.2015.02.002","article-title":"Matrix metalloproteinases in destructive lung disease","volume":"44\u201346","author":"McGarry\nHoughton","year":"2015","journal-title":"Matrix Biol."},{"key":"2026081810434535500_cit25","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/0076-6879(87)44185-2","article-title":"Proteoglycans: an overview","volume":"144","author":"Heinegard","year":"1987","journal-title":"Methods\nEnzymol."},{"key":"2026081810434535500_cit26","doi-asserted-by":"crossref","first-page":"6051","DOI":"10.1016\/S0021-9258(18)32371-8","article-title":"Purification\nof keratan sulfate proteoglycan from monkey cornea","volume":"258","author":"Nakazawa","year":"1983","journal-title":"J. Biol. Chem."},{"key":"2026081810434535500_cit27","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1080\/13506120600722530","article-title":"Lactadherin binds to elastin--a starting\npoint for medin amyloid formation?","volume":"13","author":"Larsson","year":"2006","journal-title":"Amyloid"},{"key":"2026081810434535500_cit28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1006\/abio.1999.4412","article-title":"Direct detection of crosslinks of\ncollagen and elastin in the hydrolysates of human yellow ligament\nusing single-column high performance liquid chromatography","volume":"278","author":"Chen","year":"2000","journal-title":"Anal. Biochem."},{"key":"2026081810434535500_cit29","doi-asserted-by":"publisher","first-page":"a004978","DOI":"10.1101\/cshperspect.a004978","article-title":"The collagen\nfamily","volume":"3","author":"Ricard-Blum","year":"2011","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"2026081810434535500_cit30","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1016\/S0021-9258(19)42661-6","article-title":"(Alpha1\u00ad(3))\u00ad3\nhuman skin collagen. Release by pepsin\ndigestion and preponderance in fetal life","volume":"249","author":"Epstein","year":"1974","journal-title":"J.\nBiol. Chem."},{"key":"2026081810434535500_cit31","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1006\/jtbi.2002.2542","article-title":"Mechanical implications of the domain\nstructure of fiber-forming collagens: comparison of the molecular\nand fibrillar flexibilities of the alpha1-chains found in types I-III\ncollagen","volume":"216","author":"Silver","year":"2002","journal-title":"J. Theor. Biol."},{"key":"2026081810434535500_cit32","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.1742-481X.2009.00638.x","article-title":"Hypertrophic\nversus non hypertrophic scars compared by immunohistochemistry and\nlaser confocal microscopy: type I and III collagens","volume":"6","author":"Oliveira","year":"2009","journal-title":"Int. Wound J."},{"key":"2026081810434535500_cit33","doi-asserted-by":"publisher","first-page":"128S","DOI":"10.1111\/1523-1747.ep12876104","article-title":"Fibronectin\nmatrix deposition and fibronectin receptor expression in healing and\nnormal skin","volume":"94","author":"Clark","year":"1990","journal-title":"J. Invest. Dermatol."},{"key":"2026081810434535500_cit34","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00441-009-0844-4","article-title":"Collagens","volume":"339","author":"Gordon","year":"2010","journal-title":"Cell Tissue Res."},{"key":"2026081810434535500_cit35","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1096\/fasebj.5.13.1916105","article-title":"Collagen family of proteins","volume":"5","author":"van\nder Rest","year":"1991","journal-title":"FASEB J."},{"key":"2026081810434535500_cit36","doi-asserted-by":"publisher","first-page":"M111 008128","DOI":"10.1074\/mcp.M111.008128","article-title":"Extracellular matrix composition\nand remodeling in human abdominal aortic aneurysms: a proteomics approach","volume":"10","author":"Didangelos","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"2026081810434535500_cit37","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1021\/acs.jproteome.5b00946","article-title":"Elucidating the Molecular Composition of Cartilage\nby Proteomics","volume":"15","author":"Hsueh","year":"2016","journal-title":"J. Proteome Res."},{"key":"2026081810434535500_cit38","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1074\/mcp.M000014-MCP201","article-title":"Comprehensive profiling\nof cartilage extracellular matrix formation and maturation using sequential\nextraction and label-free quantitative proteomics","volume":"9","author":"Wilson","year":"2010","journal-title":"Mol. Cell. Proteomics"},{"key":"2026081810434535500_cit39","doi-asserted-by":"publisher","first-page":"M111 014159","DOI":"10.1074\/mcp.M111.014159","article-title":"Changes\nin the chondrocyte\nand extracellular matrix proteome during post-natal mouse cartilage\ndevelopment","volume":"11","author":"Wilson","year":"2012","journal-title":"Mol. Cell. Proteomics"},{"key":"2026081810434535500_cit40","doi-asserted-by":"publisher","first-page":"233","DOI":"10.3109\/03008209809021499","article-title":"COMP (cartilage\noligomeric matrix\nprotein) is synthesized in ligament, tendon, meniscus, and articular\ncartilage","volume":"39","author":"Muller","year":"1998","journal-title":"Connect. Tissue Res."},{"key":"2026081810434535500_cit41","doi-asserted-by":"publisher","first-page":"15061","DOI":"10.1074\/jbc.M108285200","article-title":"The leucine-rich repeat\nprotein PRELP binds perlecan\nand collagens and may function as a basement membrane anchor","volume":"277","author":"Bengtsson","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026081810434535500_cit42","doi-asserted-by":"publisher","first-page":"23463","DOI":"10.1074\/jbc.273.36.23463","article-title":"A novel cartilage\nprotein (CILP) present in the mid-zone of human articular cartilage\nincreases with age","volume":"273","author":"Lorenzo","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2026081810434535500_cit43","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.biocel.2010.12.010","article-title":"The matrilins:\nmodulators of extracellular matrix assembly","volume":"43","author":"Klatt","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"issue":"Pt 2","key":"2026081810434535500_cit44","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1042\/bj3300897","article-title":"Cleavage\nof native type I collagen by human neutrophil elastase","volume":"330","author":"Kafienah","year":"1998","journal-title":"Biochem. J."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6b00806","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/15\/12\/4709\/15515372\/pr6b00806.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/15\/12\/4709\/15515372\/pr6b00806.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:29:19Z","timestamp":1787070559000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/15\/12\/4709\/1464844\/Proteomic-Analysis-of-Human-Tendon-and-Ligament"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,17]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,10,17]]},"published-print":{"date-parts":[[2016,12,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6b00806","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,17]]}}}