Mylène Jansen

326 Chapter 16 over time within an individual. SF may represent joint tissue changes more accurately than measurements from blood or urine. 21,22 We have previously investigated 7 candidate proteins in the SF of individuals after acute knee injury. These molecules were originally shown to be induced in murine knee OA in a highly mechanosensitive manner. 3 6 out of 7 proteins were found to be substantially up - regulated in those with acutely injured knees compared with controls. 23 These molecules included interleukin (IL)-6, matrix metalloproteinase (MMP)3 and monocyte chemoattractant protein (MCP)-1, associated with inflammatory activation but also others such as activin A, tumor necrosis factor-stimulated gene (TSG)-6 or tissue inhibitor of metalloproteinases (TIMP)-1, which have purported anticatabolic/anabolic roles. 24 Our preclinical work has also identified candidate chondroprotective molecules that are released by damaged cartilage including FGF-2 and TGF β . 25–27 Both of these are present in SF and have roles in chondrogenesis. 28,29 We hypothesized that over the course of KJD, changes in the joint’s mechanical environment modulate these candidate SF markers. We further hypothesized that changes in these mechanosensitive molecules either alone or in combination would be associated with clinical outcome. We set out to test these hypotheses in a proof-of-concept study in a group of individuals undergoing planned surgical KJD. Method Ethics Approval for this studywas givenby a researchethics committee (#15-160/D;NL51539.041.15). Usual care clinical data was also accessed (#17-005). All participants gave written informed consent to participate prior to screening, according to the Declaration of Helsinki. Participants Potential participants were identified by the orthopedic surgeon (RC) from a population with knee OA attending for consideration of KJD as part of their usual clinical care at a single site in Netherlands (University Medical Center Utrecht). Inclusion criteria were: age<65 years; knee OA fulfilling ACR clinical criteria 30 ; Kellgren and Lawrence (KL) grade ≥2 on radiograph 31 ; knee ligaments intact; preserved range-of-motion (flexion>120°; no loss of full extension); SF sample available at baseline. Exclusion criteria were: history of inflammatory arthritis affecting the index knee including rheumatoid arthritis; recent infection or systemic inflammatory disease; post-traumatic fibrosis; tibial plateau fracture; extensive bone-on-bone contact on X-ray; previous or planned knee arthroplasty during study period; surgery to the index knee within last 6 months; primary (isolated) patellofemoral OA; contralateral knee requiring surgical treatment; inability/contraindication/not consenting to provide SF; BMI ≥35 kg/m 2 ; pregnancy.