Osteoarthritis (OA) is a highly prevalent degenerative musculoskeletal disease and a major cause of chronic disability worldwide. Its multifactorial origin contributes to determine the heterogeneous phenotypes and one unmet need is the lack of biomarkers to predict the individual response. Platelet-rich-plasma (PRP) injection is a minimally invasive autologous blood-derived approach for which we plan to define specific knee profiles predictive of response. We will take advantage of a unique multidisciplinary approach aimed at analysing clinics, imaging, and biomarkers of associated with clinical response. We will focus on inflammatory (Wnt system, IL1 pathway, PTX3) and antioxidant (primarily, DPP3/Keap1/Nrf2) pathways. We foresee that our results will allow a better allocation of immunomodulatory and regenerative therapies for a personalized approach in knee OA thus maximising the effectiveness of the healthcare allocation.

Inclusion Criteria:

• men/women, aged >40 - <75 years), OA grade 2-3, BMI <40, baseline WOMAC PAIN >1.75 -<4, >1 conservative therapy failed. Diagnosis of knee OA according to the American College of Rheumatology (ACR) classification criteria (Altman, 1986) .
• Ability to give informed consent.

Exclusion Criteria:

• Presence of active infection or abnormal knee effusion on Day 1 at pre-injection of PRP
• Diagnosis of chronic inflammatory disease (i.e. rheumatoid arthritis, reactive arthritis, psoriatic arthritis, chondromalacia, arthritis secondary to other inflammatory diseases)
• Untreated acute traumatic injury, presence of a symptomatic meniscal tear, valgus/varus deformity judged by the investigator to be clinically significant, in the index knee
• Recent (within 3-6 months) arthroscopy, open surgery, intra-articular steroid injections, intra-articular hyaluronic acid (HA) injections, systemic steroid treatment, malignancy
• Any serious, non-malignant, significant, acute, or chronic medical condition or active psychiatric illness that, in the investigator's opinion, could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study.
• Recent (within 30 days) use of any investigational drug or device prior to screening

Knee OA patients will be enrolled at the outpatient clinic of UO1 and UO2 during the routine activity. They will receive a thorough description of the project and, if willing to participate, they will sign the informed consent. The patient number needed in the study has been calculated to ensure a proper representation of the described phenotypes (Soul J et al, 2018). The patients will undergo imaging and clinical evaluations; the respective results will be analysed and correlated with laboratory evaluations. Moreover, all patients will undergo biologic sample harvesting (as detailed below) and afterwards PRP injection. We will collect peripheral blood (PB) samples and, when available, synovial fluid (SF) from the patients prior to PRP injection