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On the Mechanisms of Action of the Low Molecular Weight Fraction of Commercial Human Serum Albumin in Osteoarthritis

机译:低分子级分的人血清白蛋白在骨关节炎中的作用机理

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摘要

The low molecular weight fraction of commercial human serum albumin (LMWF5A) has been shown to successfully relieve pain and inflammation in severe osteoarthritis of the knee (OAK). LMWF5A contains at least three active components that could account for these anti-inflammatory and analgesic effects.We summarize in vitro experiments in bone marrow–derived mesenchymal stem cells, monocytic cell lines, chondrocytes, peripheral blood mononuclear cells, fibroblast-like synoviocytes, and endothelial cells on the biochemistry of anti-inflammatory changes induced by LMWF5A. We then look at four of the major pathways that cut across cell-type considerations to examine which biochemical reactions are affected by mTOR, COX-2, CD36, and AhR pathways. All three components show anti-inflammatory activities in at least some of the cell types.The in vitro experiments show that the effects of LMWF5A in chondrocytes and bone marrow–derived stem cells in particular, coupled with recent data from previous clinical trials of single and multiple injections of LMWF5A into OAK patients demonstrated improvements in pain, function, and Patient Global Assessment (PGA), as well as high responder rates that could be attributed to the multiple mechanism of action (MOA) pathways are summarized here. In vitro and in vivo data are highly suggestive of LMWF5A being a disease-modifying drug for OAK.
机译:商业人血清白蛋白(LMWF5A)的低分子量部分已显示可成功缓解严重的膝关节骨关节炎(OAK)的疼痛和炎症。 LMWF5A至少包含三种活性成分,可以解释这些抗炎和镇痛作用。内皮细胞对LMWF5A诱导的抗炎性生化变化的影响。然后,我们查看跨越细胞类型考虑因素的四种主要途径,以检查哪些生化反应受mTOR,COX-2,CD36和AhR途径影响。所有这三个成分在至少某些细胞类型中均显示出抗炎活性。体外实验表明,LMWF5A对软骨细胞和骨髓源性干细胞的作用尤其明显,并结合了以往单项和多项临床试验的数据向OAK患者多次注射LMWF5A证明疼痛,功能和患者总体评估(PGA)有所改善,归因于多种作用机制(MOA)途径的高应答率也已在此进行了总结。体外和体内数据高度提示LMWF5A是OAK的疾病缓解药物。

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