Knee osteoarthritis (OA) in subjects over 50 years of age is a major cause of pain and impairment with a serious effect on physical activity and quality of life [16]. The present study evaluates the possible therapeutic effects of I.A injection of PRP in patients with knee OA using pain score, MOAKS and biochemical serial assays of synovial fluid cytokines levels in the form of TNF-α and MIF .
Obesity and overweight have long been recognized as important risk factors for OA, in particular knee OA [17]. The current study revealed female predominance with female: male ratio 9:1. Also, there was higher frequency for patients categorized as obesity class 1 followed by obesity class 2, while those categorized as overweight have the least frequency among patients with knee OA. These were corresponds with the findings of previous studies [18–23]. The cause of female predominance may be multifactorial and these involve structural variations, prior trauma, genetic and hormonal disorders, as men had significantly higher total tibial and patella cartilage volumes than women and women had a significantly higher prevalence of baseline patellar cartilage defects. Over time women showed more volume loss in the knee cartilage compared to their male counterparts [24]. The key but not only mechanism by which obesity will lead to knee OA is possibly increased mechanical loading on the joint. Knee overloading may cause synovial joint breakdown and failure of ligament and other structural supports [24].
While platelet-rich plasma (PRP) has been approved as an agent for knee osteoarthritis therapy, different studies of PRP in the OA knee have found more consistently positive results compared to hyaluronic acid, other intraarticular injections and placebo than in other musculoskeletal tissues [25, 26]. Although the causes of osteoarthritis in the knee are not fully understood, laboratory and clinical evidence suggest that inflammatory cytokines can contribute to its pathogenesis [27, 28]. The present study revealed significantly higher synovial fluid inflammatory cytokines (TNF-α and MIF) levels (S1, pre-injection) among patients with severe OA when compared with both mild and moderate cases with significantly lower synovial TNF-α and MIF levels two weeks after the second I.A injection of PRP (S3) in patients with mild or moderate or severe knee OA when compared with both the pre-injection synovial fluid levels and two weeks from the 1st injection (S2) levels. These indicate that PRP treatment for patients with knee osteoarthritis had beneficial effects in regulating inflammatory factors. Inflammatory cytokines have been documented to form a complex regulatory signal network in femoral head osteonecrosis which is mediated by different intracellular kinase signaling pathways to regulate the recruitment, stimulation and activation of autoimmune cells [29]. In accordance, Zhang et al [30] reported that MIF levels in synovial fluid were independently associated with the severity of self-reported pain in OA patients but not in serum. Huang et al [25] reported significantly down-regulated plasma concentrations of cytokines involving TNF-α after PRP treatment in patients with knee OA.
The current study reported significantly positive correlations between the synovial fluid TNF-α and MIF levels among the included patients with knee OA. MIF is a potent pro-inflammatory cytokine that can cause the release of many inflammatory cytokines such as interferon (IFN)-γ, interleukin (IL)-1β, 6, 8 and TNF-α by initiating an inflammatory cascade [31].
Regarding the assessments of the therapeutic effects of I.A injection of PRP on pain score and MOAKS in the included patients with knee OA, there were significantly lower mean pain score values when assessed two weeks from the second I.A injection in patients with knee OA, with significant improvement effects on synovitis and bone marrow lesions mainly for mild knee OA and to a lesser extent for moderate cases. Unfortunately, the included treated patients didn't show any significant improvements in the patella-femoral cartilage volume or meniscal disintegrity. In accordance, Burchard et al [32] suggested that intra-articular injection of PRP may improve symptoms of osteoarthritis and decrease pain in patients with knee joint osteoarthritis, independent of the level of cartilage damage quantified by the whole organ MRI scoring method. Furthermore, a study by Laudy et al [33] demonstrated that in patients with knee osteoarthritis, PRP injections resulted in decreased pain, improved function and global assessment, and changes in joint imaging.
Favorable outcome was noticed in all included patients with mild knee (100%), while it occurred in 50% of patients with moderate severity, and (20%) of patients with severe knee OA showed improvement regarding pain score. In line with our findings, Taniguchi et al [10] reported that intra-articular PRP injection is likely to be a safe treatment option for Japanese patients with mild to moderate osteoarthritis of the knee and may have pain relief for up to 6 months. While PRP therapy has controversially discussed restorative effects on the cartilage, anti-inflammatory effects, down-regulation of cytokine levels and joint homeostasis could explain favorable effects in patients with severe osteoarthritis [34, 35].
Increasing evidence shows that the over-expressed inflammatory cytokines in the inflamed joints play an important pathophysiological role in generating and maintaining OA-induced pain by acting on nociceptive nerve cells [36]. Among the included patients with knee OA, there were significantly positive correlations between synovial fluid TNF-α and MIF levels with the pain score. In consistent with our findings, Stannus et al [37] reported that TNF-α was positively linked with total knee worsening and pain.
In conclusion, the current study confirms the presence of inflammatory process involved in the pathogenesis of knee OA including involvement of some inflammatory cytokines in the form of TNF-α and MIF. Additionally, the present study confirms that among the therapeutic mechanisms of using I.A injection of PRP in patients with knee OA is the anti-inflammatory effect, where PRP may lower the synovial fluid cytokines (TNF-α and MIF) with subsequent improvement of pain and synovitis. This favorable outcome is prominently achieved in patients having mild and to a lesser extent moderate OA, thus could be established as safe adjuvant biologic therapy for such patients.