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The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang anke baranowsky Johannes Keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis

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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause anke baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment

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Bone Research 2022年第1期10卷 107-121页

作者： anke baranowsky Denise Jahn Shan Jiang Timur Yorgan Peter Ludewig Jessika Appelt Kai K.Albrecht Ellen Otto Paul Knapstein Antonia Donat Jack Winneberger Lana Rosenthal Paul Köhli Cordula Erdmann Melanie Fuchs Karl-Heinz Frosch Serafeim Tsitsilonis Michael Amling Thorsten Schinke Johannes Keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Osteology and Biomechanics University Medical Center Hamburg-EppendorfHamburg 20246Germany Center for Musculoskeletal Surgery Charité-Universitätsmedizin BerlinBerlin 13353Germany Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration Charité-Universitätsmedizin BerlinBerlin 13353Germany Department of Neurology University Medical Center Hamburg-EppendorfHamburg 20251Germany Berlin Institute of Health Berlin 10178Germany

Intermittent injections of parathyroid hormone(iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone(PTH) primarily results in increased bone resorption. Here, we identified Calca,encoding the sepsis biomarker procalcitonin(ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.

关键词： treatment representing skeleton

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