Evidence of TWIST1 and transforming growth factor-B1 aberrant expressions as novel therapeutic targets in modulating the severity of osteoarthritis with focus on biologic agents.

Osteoarthritis (OA) is marked by transcriptional factors. Twist-related protein 1 (TWIST-1) leads to the down-regulation of functional transcriptional regulators such as transforming growth factor-beta 1 (TGF-β1) and Wnt signals, thus blocking the growth and maturation of chondrocytes and providing new pathways to the production of therapeutic targets in OA therapy. Our research assesses the role of aberrant expressions TWIST1 and TGF-β1 as therapeutic targets in the regulation of osteoarthritis by treating with piperlongumine, a known biological agent. Monosodium iodoacetate (MIA) was administered to 32 male Wistar rats into their knee joints to provoke osteoarthritis. A week later, piperlongumine (PL) was orally administered to these rats for a duration of 28 days. The radiographic photos of these rats were documented. The histopathological and serum factors, namely interleukin-1beta (IL-1β), matrix metaloproteinases MMP-1 and MMP-3, were evaluated and their respective results were reported. RNA was extracted and real-time-PCR technique was optimized for TWIST1, TGF-1β and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) determination and sample values were recorded. When treated with PL at 100 mg/kg, our radiographic and histological studies revealed a substantial reduction of OA in rat models but no major improvements were observed at PL 50 mg/kg. Serum levels of IL-1β, MMP-1, and MMP-3 were greatly decreased when treated with PL 100 mg/kg. When administered with a dose higher than PL-100 mg/kg, the relative expressions of TWIST1, mRNA and TGF-β1 mRNA proteins were drastically reduced. Our results suggested that high-dose treatment with piperlongumine was beneficial and effective. TWIST1 and TGF-β1 aberrant expressions contributed as a new transcription factor function and supported the reduction of osteoarthritis intensity with piperlongumine therapy.