Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies.
BACKGROUND
Rheumatoid arthritis is a widespread autoimmune disease and inflammation and bone destruction are two main issues in rheumatoid arthritis.


OBJECTIVE
To discussing metformin effects on rheumatoid arthritis complications.


METHODS
We conducted a narrative literature search including clinical trials, experimental studies on laboratory animals and cell lines. Our search covered Medline, PubMed and Google Scholar databases from 1999 until 2018. We used the terms" Metformin; Rheumatoid arthritis; Cardiovascular disease; Cancer; Osteoblastogenesis.


DISCUSSION
Inflammatory pro-cytokines such as Interlukin-6 play important roles in T. helper 17 cell lineage differentiation. Interlukin-6 and Tumor Necrosis Factor-α activate Janus kinase receptors signal through signaling transducer and activator of transcription signaling pathway which plays important role in inflammation, bone destruction and cancer in rheumatoid arthritis patients. Interlukin-6 and Tumor Necrosis Factor-α synergistically activate signaling transducer and activator of transcription and Nuclear Factor-kβ pathways and both cytokines increase the chance of cancer development in rheumatoid arthritis patients. Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer.


CONCLUSION
Metformin effect on AMPK and mTOR pathways gives the capability to change Treg/Th17 balance and decrease Th17 differentiation and inflammation, osteoclastogenesis and cancers in RA patients. Metformin can be useful in protecting bones especially in first stages of RA and it can decrease inflammation, CVD and cancer in RA patients so Metformin beside DAMARs can be useful in increasing RA patients' life quality with less harm and cost.
['Rajaei|Elham|E|', 'Haybar|Habib|H|', 'Mowla|Karim|K|', 'Zayeri|Zeinab D|ZD|']
D000818:Animals D018501:Antirheumatic Agents D001172:Arthritis, Rheumatoid D001847:Bone Diseases D001842:Bone and Bones D002318:Cardiovascular Diseases D006801:Humans D007004:Hypoglycemic Agents D007249:Inflammation D008687:Metformin D009369:Neoplasms
Metformin medicines osteoblastogenesis cardiovascular disease rheumatoid arthritis. cancer