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      An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment

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          Abstract

          Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

          Abstract

          Osteoarthritis is a common disease that causes pain and difficulty moving joints. Here the authors present an injectable gelatin-based hydrogel that slowly releases teriparatide drug to avoid frequent injections, offering a potential solution for patients with osteoarthritis.

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          OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis

          To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data.
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            Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review

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              The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis

              Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes tend to adapt their metabolism to microenvironmental changes by shifting from one metabolic pathway to another, for example from oxidative phosphorylation to glycolysis. Similar changes occur in other joint cells, including synoviocytes. Switching between these pathways is implicated in metabolic alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, and altered lipid and amino acid metabolism. The shift between oxidative phosphorylation and glycolysis is mainly regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. Chondrocyte metabolic changes are likely to be a feature of different OA phenotypes. Determining the role of chondrocyte metabolism in OA has revealed key features of disease pathogenesis. Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of age-related OA. This knowledge will advance the development of new drugs against therapeutic targets of metabolic significance.
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                Author and article information

                Contributors
                liupeng_polymer@126.com
                yqchen0203@foxmail.com
                zenghui_36@163.com
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                31 May 2023
                31 May 2023
                2023
                : 14
                : 3159
                Affiliations
                [1 ]GRID grid.440601.7, ISNI 0000 0004 1798 0578, Department of Bone & Joint Surgery, , Peking University Shenzhen Hospital, ; Shenzhen, 518036 PR China
                [2 ]GRID grid.440601.7, ISNI 0000 0004 1798 0578, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, , Peking University Shenzhen Hospital, ; Shenzhen, 518036 PR China
                [3 ]GRID grid.412813.d, ISNI 0000 0001 0687 4946, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), , Vellore Institute of Technology (VIT), ; Vellore, Tamil Nadu 632014 India
                [4 ]GRID grid.440601.7, ISNI 0000 0004 1798 0578, Present Address: Department of Bone & Joint Surgery, , Peking University Shenzhen Hospital, ; 1120 Lianhua Road, Futian District, Shenzhen, Guangdong Province PR China
                Author information
                http://orcid.org/0000-0002-8956-5926
                http://orcid.org/0000-0002-8002-9705
                http://orcid.org/0000-0003-3121-8646
                http://orcid.org/0000-0001-6966-0769
                Article
                38597
                10.1038/s41467-023-38597-0
                10232438
                37258510
                5df929c7-f7df-4ca1-9cfd-29fb8e9126e4
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 June 2022
                : 10 May 2023
                Funding
                Funded by: This study was supported by grants from National Natural Science Foundation of China (H.Z.: 82172432; Y.Q.C.: 82202664), Guangdong Basic and Applied Basic Research Foundation (H.Z.: 2022B1515120046; P.L.: 2021A1515220037; P.L.: 2022A1515220165), Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research (H.Z., Y.Q.C., P.L., J.W., and F.Y.: ZDSYS20220606100602005), “San-Ming” Project of Medicine in Shenzhen (H.Z., and D.L.W: SZSM201612092) and Shenzhen Science and Technology Program (H.Z.: JCYJ20220818102815033, KCXFZ20201221173411031, JCYJ20210324110214040 and P.L.: JCYJ20210324105806016). We would also like to thank the Department of Bone and Joint Surgery, Department of Pathology, and Central Laboratory of Peking University Shenzhen Hospital.
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                © Springer Nature Limited 2023

                Uncategorized
                translational research,parathyroid hormone,biomedical materials,drug delivery,biomedical engineering

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