{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:12:51Z","timestamp":1792930371897,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Elements of the project are financed by the European Commission's Framework Program 7","award":["Bio-NMR; project number 261863"],"award-info":[{"award-number":["Bio-NMR; project number 261863"]}]},{"name":"National Natural Science Foundation of China","award":["No. 82001286"],"award-info":[{"award-number":["No. 82001286"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong province","doi-asserted-by":"publisher","award":["No.ZR2020QH112"],"award-info":[{"award-number":["No.ZR2020QH112"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Operational Programme Integrated Infrastructure, funded by the ERDF","award":["ITMS2014+: 313011V455"],"award-info":[{"award-number":["ITMS2014+: 313011V455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.<\/jats:p>","DOI":"10.3390\/md19100542","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T04:55:33Z","timestamp":1632718533000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms"],"prefix":"10.3390","volume":"19","author":[{"given":"Thomas","family":"Eckert","sequence":"first","affiliation":[{"name":"RI-B-NT\u2014Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany"},{"name":"Institut f\u00fcr Veterin\u00e4rphysiolgie und Biochemie, Fachbereich Veterin\u00e4rmedizin, Justus-Liebig-Universit\u00e4t Gie\u00dfen, Frankfurter Str. 100, 35392 Gie\u00dfen, Germany"},{"name":"Department of Chemistry and Biology, University of Applied Sciences Fresenius, Limburger Str. 2, 65510 Idstein, Germany"},{"name":"RISCC\u2014Research Institute for Scientific Computing and Consulting, Ludwig-Schunk-Str. 15, 35452 Heuchelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahena","family":"J\u00e4hrling-Butkus","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Veterin\u00e4rphysiolgie und Biochemie, Fachbereich Veterin\u00e4rmedizin, Justus-Liebig-Universit\u00e4t Gie\u00dfen, Frankfurter Str. 100, 35392 Gie\u00dfen, Germany"},{"name":"Tierarztpraxis Dr. Silke Fritscher, Bergstra\u00dfe 104, 73441 Bopfingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-823X","authenticated-orcid":false,"given":"Helen","family":"Louton","sequence":"additional","affiliation":[{"name":"Animal Health and Animal Welfare, Faculty of Agricultural and Environmental Sciences, University of Rostock, Justus-von-Liebig-Weg 6b, 18059 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Burg-Roderfeld","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Veterin\u00e4rphysiolgie und Biochemie, Fachbereich Veterin\u00e4rmedizin, Justus-Liebig-Universit\u00e4t Gie\u00dfen, Frankfurter Str. 100, 35392 Gie\u00dfen, Germany"},{"name":"Department of Chemistry and Biology, University of Applied Sciences Fresenius, Limburger Str. 2, 65510 Idstein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-9539","authenticated-orcid":false,"given":"Ruiyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"RI-B-NT\u2014Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany"},{"name":"Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-8611","authenticated-orcid":false,"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"RI-B-NT\u2014Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany"},{"name":"Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Hesse","sequence":"additional","affiliation":[{"name":"Tierarztpraxis Dr. Karsten Hesse, Rathausstra\u00dfe 16, 35460 Staufenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-5281","authenticated-orcid":false,"given":"Athanasios K.","family":"Petridis","sequence":"additional","affiliation":[{"name":"Medical School, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Universit\u00e4tsstr. 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-1791","authenticated-orcid":false,"given":"Tibor","family":"Ko\u017e\u00e1r","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. 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Ausgabe K Kleintiere\/Heimtiere"},{"key":"ref_2","unstructured":"Bockstahler, B., Levine, D., Millis, D.L., and Wandrey, S.O.N. (2004). Essential Facts of Physiotherapy in Dogs and Cats, BE VetVerlag."},{"key":"ref_3","first-page":"20","article-title":"Production of Glucosamine Hydrochloride from Crustacean Shell","volume":"3","author":"Benavente","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s13238-010-0038-6","article-title":"Interaction of the alpha2A domain of integrin with small collagen fragments","volume":"1","author":"Siebert","year":"2010","journal-title":"Protein Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s11172-011-0115-x","article-title":"Preliminary structural characterization, anti-inflammatory and anticoagulant activities of chondroitin sulfates from marine fish cartilage","volume":"60","author":"Krylov","year":"2011","journal-title":"Russian Chem. Bull."},{"key":"ref_6","first-page":"36","article-title":"Bioaktive Kollagenfragmente. Neue struktur-biologische Studien an Kollagen-Integrin-Komplexen belegen Justus Liebigs wegweisende Ideen","volume":"28","author":"Eckert","year":"2011","journal-title":"Spiegel der Forschung"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1002\/cphc.201200284","article-title":"Molecular organization of various collagen fragments as revealed by atomic force microscopy and diffusion-ordered NMR spectroscopy","volume":"13","author":"Schurink","year":"2012","journal-title":"ChemPhysChem"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Schadow, S., Simons, V.S., Lochnit, G., Kordelle, J., Gazova, Z., Siebert, H.C., and Steinmeyer, J. (2017). Metabolic Response of Human Osteoarthritic Cartilage to Biochemically Characterized Collagen Hydrolysates. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010207"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schadow, S., Siebert, H.C., Lochnit, G., Kordelle, J., Rickert, M., and Steinmeyer, J. (2013). Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053955"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00418-010-0760-4","article-title":"Hydrolyzed fish collagen induced chondrogenic differentiation of equine adipose tissue-derived stromal cells","volume":"134","author":"Raabe","year":"2010","journal-title":"Histochem Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1073\/pnas.0407106102","article-title":"Conformational variability of matrix metalloproteinases: Beyond a single 3D structure","volume":"102","author":"Bertini","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1110\/ps.073287008","article-title":"Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS-5","volume":"17","author":"Mosyak","year":"2008","journal-title":"Protein Sci. Publ. Protein Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00775-007-0288-9","article-title":"Matrix metalloproteinase-inhibitor interaction: The solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors","volume":"12","author":"Alcaraz","year":"2007","journal-title":"J. Biol. Inorg. Chem. JBIC Publ. Soc. Biol. Inorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s000110050742","article-title":"Effects of tetracyclines on the production of matrix metalloproteinases and plasminogen activators as well as of their natural inhibitors, tissue inhibitor of metalloproteinases-1 and plasminogen activator inhibitor-1","volume":"50","author":"Sadowski","year":"2001","journal-title":"Inflamm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/srep00717","article-title":"Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides","volume":"2","author":"Masuyer","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"648537","DOI":"10.1155\/2012\/648537","article-title":"Expression of Angiotensin II Receptor-1 in Human Articular Chondrocytes","volume":"2012","author":"Kawakami","year":"2012","journal-title":"Arthritis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1002\/2211-5463.12438","article-title":"Cyclic compressive loading activates angiotensin II type 1 receptor in articular chondrocytes and stimulates hypertrophic differentiation through a G-protein-dependent pathway","volume":"8","author":"Nakamura","year":"2018","journal-title":"FEBS Open Bio"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1271\/bbb.120718","article-title":"Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure","volume":"77","author":"Kouguchi","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kosinska, M.K., Ludwig, T.E., Liebisch, G., Zhang, R., Siebert, H.C., Wilhelm, J., Kaesser, U., Dettmeyer, R.B., Klein, H., and Ishaque, B. (2015). Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125192"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2746\/042516406775374306","article-title":"Evaluation of glucosamine levels in commercial equine oral supplements for joints","volume":"38","author":"Oke","year":"2006","journal-title":"Equine Vet. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4236\/ojpc.2012.22017","article-title":"In silico Study on Sulfated and Non-Sulfated Carbohydrate Chains from Proteoglycans in Cnidaria and Interaction with Collagen","volume":"2","author":"Eckert","year":"2012","journal-title":"Open J. Phys. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1021\/ja904334s","article-title":"Why Structurally Different Cyclic Peptides Can Be Glycomimetics of the HNK-1 Carbohydrate Antigen","volume":"132","author":"Bhunia","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1021\/ja2083015","article-title":"Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. The specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and STD NMR","volume":"134","author":"Tsvetkov","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.joca.2009.09.004","article-title":"Phenotype-related differential alpha-2,6- or alpha-2,3-sialylation of glycoprotein N-glycans in human chondrocytes","volume":"18","author":"Toegel","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","first-page":"1","article-title":"Exploration of the Sialic Acid World","volume":"75","author":"Schauer","year":"2018","journal-title":"Adv. Carb. Chem. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1002\/cmdc.201500609","article-title":"Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides","volume":"11","author":"Zhang","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_27","first-page":"1","article-title":"Interaction studies of sialic acids with model receptors contribute to nanomedical therapies","volume":"3","author":"Siebert","year":"2015","journal-title":"J. Neurol. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/j.carres.2009.06.002","article-title":"A lectin from the Chinese bird-hunting spider binds sialic acids","volume":"344","author":"Siebert","year":"2010","journal-title":"Carbohydr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1017\/S0033583517000075","article-title":"Lysozyme\u2019s lectin-like characteristics facilitates its immune defense function","volume":"50","author":"Zhang","year":"2017","journal-title":"Q. Rev. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2174\/1568026615666150703120753","article-title":"Structure-Function Relationships of Antimicrobial Peptides and Proteins with Respect to Contact Molecules on Pathogen Surfaces","volume":"16","author":"Zhang","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1021\/acs.biomac.6b00165","article-title":"Evidence for Inhibition of Lysozyme Amyloid Fibrillization by Peptide Fragments from Human Lysozyme: A Combined Spectroscopy, Microscopy, and Docking Study","volume":"17","author":"Kar","year":"2016","journal-title":"Biomacromolecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/jn\/129.10.1891","article-title":"Oral administration of (14)C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57\/BL)","volume":"129","author":"Oesser","year":"1999","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00441-003-0702-8","article-title":"Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen","volume":"311","author":"Oesser","year":"2003","journal-title":"Cell Tissue Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"254","DOI":"10.4236\/ojas.2017.73020","article-title":"The Effectiveness of Specific Collagen Peptides on Osteoarthritis in Dogs-Impact on Metabolic Processes in Canine Chondrocytes","volume":"07","author":"Schunck","year":"2017","journal-title":"Open J. Anim. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/jpn.12863","article-title":"Specific bioactive collagen peptides (PETAGILE((R))) as supplement for horses with osteoarthritis: A two-centred study","volume":"102","author":"Dobenecker","year":"2018","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17733","DOI":"10.1038\/s41598-018-36046-3","article-title":"Comparative Analysis of Peptide Composition and Bioactivity of Different Collagen Hydrolysate Batches on Human Osteoarthritic Synoviocytes","volume":"8","author":"Simons","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1590\/1809-9823.2016.14145","article-title":"Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: A systematic review","volume":"19","author":"Fanaro","year":"2016","journal-title":"Revista Brasileira de Geriatria e Gerontologia"},{"key":"ref_38","first-page":"469","article-title":"Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV","volume":"80","author":"Li","year":"2020","journal-title":"J. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Saponaro, F., Rutigliano, G., Sestito, S., Bandini, L., Storti, B., Bizzarri, R., and Zucchi, R. (2020). ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.588618"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16471","DOI":"10.1038\/s41598-020-71936-5","article-title":"SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals","volume":"10","author":"Lam","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1039\/C9FO02944C","article-title":"Amelioration of clinical course and demyelination in the cuprizone mouse model in relation to ketogenic diet","volume":"11","author":"Zhang","year":"2020","journal-title":"Food Funct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1021\/acsomega.9b03702","article-title":"Influence of Long-Chain\/Medium-Chain Triglycerides and Whey Protein\/Tween 80 Ratio on the Stability of Phosphatidylserine Emulsions (O\/W)","volume":"5","author":"Zhang","year":"2020","journal-title":"ACS Omega"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, R., Jin, L., Zhang, N., Petridis, A.K., Eckert, T., Scheiner-Bobis, G., Bergmann, M., Scheidig, A., Schauer, R., and Yan, M. (2019). The Sialic Acid-Dependent Nematocyst Discharge Process in Relation to Its Physical-Chemical Properties Is A Role Model for Nanomedical Diagnostic and Therapeutic Tools. Mar. Drugs, 17.","DOI":"10.3390\/md17080469"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1021\/acsomega.8b02471","article-title":"Nanomedical Relevance of the Intermolecular Interaction Dynamics-Examples from Lysozymes and Insulins","volume":"4","author":"Zhang","year":"2019","journal-title":"ACS Omega"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1055\/s-0034-1381772","article-title":"Epidemiologie der Osteoarthritis-Osteoarthrose(OA)","volume":"17","author":"Mele","year":"2007","journal-title":"Vet. Focus"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tvjl.2015.07.016","article-title":"Quality of life assessment in domestic dogs: An evidence-based rapid review","volume":"206","author":"Belshaw","year":"2015","journal-title":"Vet. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/ilar.44.3.197","article-title":"Assessment of pain in dogs: Veterinary clinical studies","volume":"44","author":"Hansen","year":"2003","journal-title":"ILAR J."},{"key":"ref_48","first-page":"1552","article-title":"Evaluation of methods for assessment of painassociated with chronic osteoarthritis in dogs","volume":"11","author":"Kuusela","year":"2003","journal-title":"JAVMA"},{"key":"ref_49","unstructured":"Weide, N. (2004). The Application of Gelatinehydrolysate in Clinical Orthopedic Healthy Dogs and Dogs with Chronic Defects on the Locomotor System, Tier\u00e4rztliche Hochschule."},{"key":"ref_50","unstructured":"Hielm-Bj\u00f6rkman, A. (2007). Assessment of Chronic Pain and Evaluation of Three Complementary Therapies (Gold Implants, Green Lipped Mussel and a Homeopathic Combination Preparation) for Canine Osteoarthritis, Using Ran Domized, Controlled, Double-Blind Study Designs, Ubiversity of Helsinki."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"305","DOI":"10.56808\/2985-1130.2739","article-title":"Ameliorative Effects of Omega-3 Concentrate in Managing Coxofemoral Osteoarthritic Pain in Dogs","volume":"46","author":"Sastravaha","year":"2016","journal-title":"Thai. J. Vet. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.1038\/sj.onc.1206834","article-title":"Ras oncogene directs expression of a differentially sialylated, functionally altered beta1 integrin","volume":"22","author":"Seales","year":"2003","journal-title":"Oncogene"},{"key":"ref_53","first-page":"1109","article-title":"Physical and functional cooperation of neural cell adhesion molecule and beta1-integrin in neurite outgrowth induction","volume":"18","author":"Petridis","year":"2011","journal-title":"J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australas."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s13238-017-0377-7","article-title":"The minor collagens in articular cartilage","volume":"8","author":"Luo","year":"2017","journal-title":"Protein Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12501","DOI":"10.1074\/jbc.C000848200","article-title":"TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5)","volume":"276","author":"Kashiwagi","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Parkkonen, O., Nieminen, M.T., Vesterinen, P., Tervahartiala, T., Perola, M., Salomaa, V., Jousilahti, P., Sorsa, T., Pussinen, P.J., and Sinisalo, J. (2017). Low MMP-8\/TIMP-1 reflects left ventricle impairment in takotsubo cardiomyopathy and high TIMP-1 may help to differentiate it from acute coronary syndrome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173371"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1080\/09168451.2020.1792763","article-title":"Sialic acid sulfation is induced by the antibiotic treatment in mammalian cells","volume":"84","author":"Ertunc","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_58","unstructured":"Dixon, W.J. (1993). BMDP Statistical Software Manual, University of California Press."},{"key":"ref_59","unstructured":"(2010). Cytel Studio StatXact, Cytel Software Corporation."},{"key":"ref_60","unstructured":"Schr\u00f6dinger (2020). Maestro, v. 12.3.013, Schr\u00f6dinger, LLC."},{"key":"ref_61","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian 09, Gaussian, Inc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jmb.2006.07.014","article-title":"Conformational effects of Gly-X-Gly interruptions in the collagen triple helix","volume":"362","author":"Bella","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1747-0285.2007.00483.x","article-title":"New method for fast and accurate binding-site identification and analysis","volume":"69","author":"Halgren","year":"2007","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_64","unstructured":"Schr\u00f6dinger (2013). SiteMap, Version 3.9, Schr\u00f6dinger, LLC."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_68","unstructured":"Schr\u00f6dinger (2013). Glide, Version 6.1, Schr\u00f6dinger, LLC."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/prot.10379","article-title":"Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2","volume":"52","author":"Ritchie","year":"2003","journal-title":"Proteins"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Sacerdoti, F.D., Salmon, J.K., Shan, Y., Shaw, D.E., Chow, E., Xu, H., Dror, R.O., Eastwood, M.P., and Gregersen, B.A. (2006, January 11\u201317). Molecular dynamics\u2014Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing\u2014SC \u201906, Tampa, FL, USA.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1021\/ja00214a001","article-title":"The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin","volume":"110","author":"Jorgensen","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.1073\/pnas.0408037102","article-title":"Potential energy functions for atomic-level simulations of water and organic and biomolecular systems","volume":"102","author":"Jorgensen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6269","DOI":"10.1021\/j100308a038","article-title":"The Missing Term in Effective Pair Potentials","volume":"91","author":"Berendsen","year":"1987","journal-title":"J. Phys. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gkv315","article-title":"PLIP: Fully automated protein-ligand interaction profiler","volume":"43","author":"Salentin","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/10\/542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:05:20Z","timestamp":1760166320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/10\/542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,26]]},"references-count":74,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["md19100542"],"URL":"https:\/\/doi.org\/10.3390\/md19100542","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,26]]}}}