Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient's quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Keywords: chondrocytes; cytokines; knee; osteoarthritis; platelet-rich plasma.

Figure 1

Profiles of cytokines, chemokines, and growth factors in PRP and PPP of knee OA patients at various concentrations: (A) 0–1.5 pg/mL; (B) 1.5–15 pg/mL; (C) 15–80 pg/mL; (D) 100–30,000 pg/mL. Abbreviations: OA, osteoarthritis; PRP, platelet-rich plasma; PPP, platelet-poor plasma. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 2

Effects of PRP, PPP, and FBS on migration and proliferation of OA chondrocytes: (A) scratch assay images captured at 0, 24, and 48 h using an inverted light microscope to observe migration of knee OA chondrocytes; (B) migration of knee OA chondrocytes cultured with PRP, PPP, and FBS at 0, 24, and 48 h; (C) proliferation of knee OA chondrocytes cultured with PRP, PPP and FBS at 0, 3, 6, and 9 h. Abbreviations: FBS, fetal bovine serum; OA, osteoarthritis; PRP, platelet-rich plasma; PPP, platelet-poor plasma.

Figure 3

Effects of PRP, PPP, and FBS on expressions of cartilage-specific genes in knee OA chondrocytes: (A) relative SOX9 mRNA expression; (B) relative COL2A1 mRNA expression; (C) relative ACAN mRNA expression. Abbreviations: ACAN, aggrecan; COL2A1, collagen type II alpha 1; FBS, fetal bovine serum; OA, osteoarthritis; PRP, platelet-rich plasma; PPP, platelet-poor plasma; SOX9, SRY-box transcription factor.

Figure 4

Comparison of physical performance at 0 and 18 weeks following intra-articular PRP injection in knee OA patients: (A) sit to stand; (B) time up to go; (C) 3 min walk test.

Figure 5

Comparison of WOMAC score at 0 and 18 weeks following intra-articular PRP injection in knee OA patients: (A) pain; (B) stiffness; (C) physical function; (D) total score. Abbreviations: WOMAC, Western Ontario and McMaster Universities Osteoarthritis.