Therapeutic Nanodiamonds Containing Icariin Ameliorate the Progression of Osteoarthritis in Rats

Abstract

In present study, icariin (ICA)/tannic acid (TA)-nanodiamonds (NDs) were prepared as follows. ICA was anchored to ND surfaces with absorbed TA (ICA/TA-NDs) and we evaluated their in vitro anti-inflammatory effects on lipopolysaccharide (LPS)-activated macrophages and in vivo cartilage protective effects on a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The ICA/TA-NDs showed prolonged release of ICA from the NDs for up to 28 days in a sustained manner. ICA/TA-NDs inhibited the mRNA levels of pro-inflammatory elements, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and increased the mRNA levels of anti-inflammatory factors (i.e., IL-4 and IL-10) in LPS-activated RAW 264.7 macrophages. Animal studies exhibited that intra-articular injection of ICA/TA-NDs notably suppressed levels of IL-6, MMP-3, and TNF-α and induced level of IL-10 in serum of MIA-induced OA rat models in a dose-dependent manner. Furthermore, these noticeable anti-inflammatory effects of ICA/TA-NDs remarkably contributed to the protection of the progression of MIA-induced OA and cartilage degradation, as exhibited by micro-computed tomography (micro-CT), gross findings, and histological investigations. Accordingly, in vitro and in vivo findings suggest that the prolonged ICA delivery of ICA/TA-NDs possesses an excellent latent to improve inflammation as well as defend against cartilage disorder in OA.