Bar-Or David, Thomas Gregory, Rael Leonard T, Frederick Elizabeth, Hausburg Melissa, Bar-Or Raphael, Brody Edward
Trauma Research Department, Swedish Medical Center, 501 E. Hampden Avenue, Englewood, CO 80113, United States.
Trauma Research Department, St. Anthony Hospital, 1600 W. 2nd Place, Lakewood, CO 80228, United States.
Curr Rheumatol Rev. 2019;15(3):189-200. doi: 10.2174/1573397114666181119121519.
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 antiinflammatory 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.
已证明商业人血清白蛋白的低分子量部分（LMWF5A）能成功缓解重度膝骨关节炎（OAK）的疼痛和炎症。LMWF5A含有至少三种活性成分，这些成分可能是其抗炎和镇痛作用的原因。我们总结了在骨髓间充质干细胞、单核细胞系、软骨细胞、外周血单核细胞、成纤维样滑膜细胞和内皮细胞中进行的体外实验，这些实验涉及LMWF5A诱导的抗炎变化的生物化学过程。然后，我们研究了跨越细胞类型考虑因素的四个主要途径，以检查哪些生化反应受mTOR、COX - 2、CD36和AhR途径的影响。所有三种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尤其在软骨细胞和骨髓来源的干细胞中具有作用，再结合先前对OAK患者单次和多次注射LMWF5A的临床试验的最新数据，显示出疼痛、功能和患者整体评估（PGA）有所改善，以及高反应率，这些都可归因于多种作用机制（MOA）途径，本文对此进行了总结。体外和体内数据都强烈表明LMWF5A是一种用于OAK的疾病改善药物。
