PMID- 36045373 OWN - NLM STAT- MEDLINE DCOM- 20220907 LR - 20220907 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 17 IP - 1 DP - 2022 Aug 31 TI - Intra-bone marrow injection of magnesium isoglyrrhizinate inhibits inflammation and delays osteoarthritis progression through the NF-kappaB pathway. PG - 400 LID - 10.1186/s13018-022-03294-z [doi] LID - 400 AB - OBJECTIVE: Osteoarthritis (OA) presents cartilage damage in addition to chronic inflammation. However, self-recovery of damaged cartilage in an inflammatory environment is not possible. Mesenchymal stem cells (MSCs) in the bone marrow are a source of regenerative repair of damaged cartilage. To date, whether intra-luminal administration of the bone marrow can delay the progression of OA is still unknown. This study, therefore, aimed to explore the role of intra-bone marrow injection of Magnesium isoglycyrrhizinate (MgIG) in delaying the OA progression and to investigate the underlying mechanism. METHODS: Rabbit OA models were established using the anterior cruciate ligament transection method while a catheter was implanted into the bone marrow cavity. 1 week after surgery, MgIG treatment was started once a week for 4 weeks. The cartilage degradation was analyzed using hematoxylin-eosin staining, Masson's trichrome staining and Alcian blue staining. Additionally, the pro-inflammatory factors and cartilage regeneration genes involved in the cartilage degeneration and the underlying mechanisms in OA were detected using enzyme-linked immunosorbent assay, quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: The results of histological staining revealed that intra-bone marrow injection of MgIG reduced degeneration and erosion of articular cartilage, substantially reducing the Osteoarthritis Research Society International scores. Furthermore, the productions of inflammatory cytokines in the bone marrow cavity and articular cavity such as interleukin-1beta(IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were inhibited upon the treatment of MgIG. At the same time, the expression of alkaline phosphate, tartrate-resistant acid phosphatase-5b (TRAP-5b) and C-telopeptides of type II collagen (CTX-II) in the blood also decreased and was positively correlated. On the contrary, cartilage-related genes in the bone marrow cavity such as type II collagen (Col II), Aggrecan (AGN), and SRY-box 9 (SOX9) were up-regulated, while matrix metalloproteinase-3 (MMP-3) was down-regulated. Mechanistically, MgIG was found to exert an anti-inflammatory effect and impart protection to the cartilage by inhibiting the NF-kappaB pathway. CONCLUSION: Intra-bone marrow injection of MgIG might inhibit the activation of the NF-kappaB pathway in the progression of OA to exert an anti-inflammatory effect in the bone marrow cavity and articular cavity, thereby promoting cartilage regeneration of MSCs in the bone marrow, making it a potential new therapeutic intervention for the treatment of OA. CI - (c) 2022. The Author(s). FAU - Chen, Rong AU - Chen R AD - Department of Traumatic Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China. FAU - Li, Xiangwei AU - Li X AD - Department of Traumatic Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China. FAU - Sun, Zhibo AU - Sun Z AD - Department of Traumatic Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China. FAU - Yin, Junyi AU - Yin J AD - Hubei Key Laboratory of Embryonic Stem Cell Research, Department of Anatomy, School of Basic Medical Sciences, Hubei University of Medicine, No. 30 Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. FAU - Hu, Xiaowei AU - Hu X AD - Hubei Key Laboratory of Embryonic Stem Cell Research, Department of Anatomy, School of Basic Medical Sciences, Hubei University of Medicine, No. 30 Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. FAU - Deng, Jingwen AU - Deng J AD - Hubei Key Laboratory of Embryonic Stem Cell Research, Department of Anatomy, School of Basic Medical Sciences, Hubei University of Medicine, No. 30 Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. FAU - Liu, Xinghui AU - Liu X AD - Department of Traumatic Orthopedics, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China. 403758354@qq.com. AD - Hubei Key Laboratory of Embryonic Stem Cell Research, Department of Anatomy, School of Basic Medical Sciences, Hubei University of Medicine, No. 30 Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China. 403758354@qq.com. LA - eng GR - 21Y47/Scientific and Technological Project of Shiyan City of Hubei Province/ GR - X202110929012/Undergraduate Training Programs for Innovation and Entrepreneurship of Hubei University of Medicine/ GR - WJ2019F064/Health Commission of Hubei Province/ GR - 2015QDZR11/Cultivating Project for Young Scholar at Hubei University of Medicine/ PT - Journal Article DEP - 20220831 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Collagen Type II) RN - 0 (Interleukin-1beta) RN - 0 (NF-kappa B) RN - I38ZP9992A (Magnesium) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Bone Marrow MH - *Cartilage, Articular/metabolism MH - Chondrocytes/metabolism MH - Collagen Type II/metabolism MH - Disease Models, Animal MH - Inflammation/drug therapy/metabolism/prevention & control MH - Interleukin-1beta/metabolism MH - Magnesium/metabolism MH - NF-kappa B/metabolism MH - *Osteoarthritis/pathology MH - Rabbits PMC - PMC9429748 OTO - NOTNLM OT - Cartilage regeneration OT - Intra-bone marrow injection OT - Magnesium isoglycyrrhizinate OT - NF-kappaB OT - Osteoarthritis COIS- The authors declare that they have no competing interests. EDAT- 2022/09/01 06:00 MHDA- 2022/09/08 06:00 PMCR- 2022/08/31 CRDT- 2022/08/31 23:33 PHST- 2022/06/27 00:00 [received] PHST- 2022/08/18 00:00 [accepted] PHST- 2022/08/31 23:33 [entrez] PHST- 2022/09/01 06:00 [pubmed] PHST- 2022/09/08 06:00 [medline] PHST- 2022/08/31 00:00 [pmc-release] AID - 10.1186/s13018-022-03294-z [pii] AID - 3294 [pii] AID - 10.1186/s13018-022-03294-z [doi] PST - epublish SO - J Orthop Surg Res. 2022 Aug 31;17(1):400. doi: 10.1186/s13018-022-03294-z.