{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:38Z","timestamp":1792804778213,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chonnam National University Hwasun Hospital Institute for Biomedical Science","award":["HCRI 19 001-1* 21013"],"award-info":[{"award-number":["HCRI 19 001-1* 21013"]}],"id":[{"id":"https:\/\/ror.org\/054gh2b75","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Chonnam National University Hwasun Hospital Institute for Biomedical Science","award":["22C0603L1-11"],"award-info":[{"award-number":["22C0603L1-11"]}],"id":[{"id":"https:\/\/ror.org\/054gh2b75","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Korea Fund for Regenerative Medicine (KFRM)","award":["HCRI 19 001-1* 21013"],"award-info":[{"award-number":["HCRI 19 001-1* 21013"]}]},{"name":"Korea Fund for Regenerative Medicine (KFRM)","award":["22C0603L1-11"],"award-info":[{"award-number":["22C0603L1-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1\u03b2 (IL-1\u03b2) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1\u03b2 on chondrocytes. We stimulated chondrocytes with IL-1\u03b2 to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1\u03b2 on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-\u03baB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1\u03b2 on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.<\/jats:p>","DOI":"10.3390\/ijms25137263","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1\u03b2-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-6062","authenticated-orcid":false,"given":"Jaishree","family":"Sankaranarayanan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-6324","authenticated-orcid":false,"given":"Sree Samanvitha","family":"Kuppa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Keun","family":"Seon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup 519763, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shigley, C., Trivedi, J., Meghani, O., Owens, B.D., and Jayasuriya, C.T. 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