{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:27:33Z","timestamp":1784608053935,"version":"3.55.0"},"reference-count":116,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Padova \u201cFONDO DOR\u2014Bando 2021\u2014Di Liddo Rosa\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucosamine (GlcN) is a glycosaminoglycan (GAGs) constituent in connective tissues. It is naturally produced by our body or consumed from diets. In the last decade, in vitro and in vivo trials have demonstrated that the administration of GlcN or its derivates has a protective effect on cartilage when the balance between catabolic and anabolic processes is disrupted and cells are no longer able to fully compensate for the loss of collagen and proteoglycans. To date, these benefits are still controversial because the mechanism of action of GlcN is not yet well clarified. In this study, we have characterized the biological activities of an amino acid (AA) derivate of GlcN, called DCF001, in the growth and chondrogenic induction of circulating multipotent stem cells (CMCs) after priming with tumor necrosis factor-alpha (TNF\u03b1), a pleiotropic cytokine commonly expressed in chronic inflammatory joint diseases. In the present work, stem cells were isolated from the human peripheral blood of healthy donors. After priming with TNF\u03b1 (10 ng\/mL) for 3 h, cultures were treated for 24 h with DCF001 (1 \u03bcg\/mL) dissolved in a proliferative (PM) or chondrogenic (CM) medium. Cell proliferation was analyzed using a Corning\u00ae Cell Counter and trypan blue exclusion technique. To evaluate the potentialities of DCF001 in counteracting the inflammatory response to TNF\u03b1, we measured the amount of extracellular ATP (eATP) and the expression of adenosine-generating enzymes CD39\/CD73, TNF\u03b1 receptors, and NF-\u03baB inhibitor I\u03baB\u03b1 using flow cytometry. Finally, total RNA was extracted to perform a gene expression study of some chondrogenic differentiation markers (COL2A1, RUNX2, and MMP13). Our analysis has shed light on the ability of DCF001 to (a) regulate the expression of CD39, CD73, and TNF receptors; (b) modulate eATP under differentiative induction; (c) enhance the inhibitory activity of I\u03baB\u03b1, reducing its phosphorylation after TNF\u03b1 stimulation; and (d) preserve the chondrogenic potentialities of stem cells. Although preliminary, these results suggest that DCF001 could be a valuable supplement for ameliorating the outcome of cartilage repair interventions, enhancing the efficacy of endogenous stem cells under inflammatory stimuli.<\/jats:p>","DOI":"10.3390\/ijms241210397","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T01:35:11Z","timestamp":1687311311000},"page":"10397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of Modified Glucosamine on the Chondrogenic Potential of Circulating Stem Cells under Experimental Inflammation"],"prefix":"10.3390","volume":"24","author":[{"given":"Marco","family":"Gasparella","sequence":"first","affiliation":[{"name":"Local Health Unit Treviso, Department of Pediatric Surgery, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-3444","authenticated-orcid":false,"given":"Carola","family":"Cenzi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-1960","authenticated-orcid":false,"given":"Monica","family":"Piccione","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-612X","authenticated-orcid":false,"given":"Valentina Noemi","family":"Madia","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technology, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4279-7666","authenticated-orcid":false,"given":"Roberto","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technology, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Tudino","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technology, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-7007","authenticated-orcid":false,"given":"Marco","family":"Artico","sequence":"additional","affiliation":[{"name":"Department of Sensory Organs, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Taurone","sequence":"additional","affiliation":[{"name":"Department of Movement, Human and Health Sciences-Division of Health Sciences, University of Rome \u201cForo Italico\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"De Ponte","sequence":"additional","affiliation":[{"name":"Department of Sensory Organs, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Costi","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technology, University of Rome \u201cLa Sapienza\u201d, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-6804","authenticated-orcid":false,"given":"Rosa","family":"Di Liddo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.joca.2007.01.019","article-title":"Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose","volume":"15","author":"Persiani","year":"2007","journal-title":"Osteoarthr. 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