Background Midkine is a heparin-binding growth factor that plays an important role in mesoderm remodeling as in chondrogenesis and adipocyte formation. There is an increased expression of midkine in damaged tissues and it is believed to have functional antagonism, as it helps in tissue repair and survival while, on the other hand it can enhance inflammatory reactions resulting in more tissue injury .
Objectives This study aimed to determine serum and synovial fluid (SF) levels of midkine in patients with primary knee osteoarthritis (KOA) and to examine the relationship between these levels with the clinical and functional parameters as well as radiological progression of KOA.
Methods We measured midkne in the serum (n=52) and SF samples (n=23) from 52 KOA patients as well as in the serum from 20 healthy control (n=20). In the patients, numerical rating scale of pain (NRSP), body mass index (BMI) and The Western Ontario Mc Master scale (WOMAC) were recorded. Graded plain radiographs using Thomas score, and musculoskeletal ultrasound examination (MSUS) of both knees were performed at baseline and after 24 months to assess radiological progression [2,3]. Radiological progression was considered if there is an increase in the Thomas grading score or MSUS transition to a higher grade at the 24 months follow up period compared to baseline evaluation.
Results Serum and SF midkine levels were significantly increased in KOA patients (mean ± SD 80.79±31.8 pg/mL and 216.31±94.93 pg/mL respectively) compared to serum level in the healthy controls (mean ± SD 65.6±14.76 pg/mL),p<0.05 and p<0.001 respectively. In KOA patients, the serum and SF concentrations of midkine significantly correlated with the baseline thickness of the cartilage on the medial condyle (r= −0.41 and -0.52 respectively, p<0.05) but not on the lateral condyle of the femur (r=0.12 and 0.15 respectively, p>0.05). Patients with elevated serum and SF midkine (defined as midkine level more than the mean plus 2 standard deviation of healthy controls's level) had a twofold increased risk of radiological progression with MSUS (age, sex and BMI adjusted RR 2.4 and 2.6, 95% CI respectively).With elevated serum and SF midkine levels, there was no increased risk of radiological progression detected with plain radiography in KOA Patients (age, sex and BMI adjusted RR 1.3 and 1.6, 95% CI respectively).
Conclusions Osteoarthritis patients have significantly elevated serum and synovial levels of midkine that were obviously associated with radiological progression on MSUS suggesting that it could be a useful marker to reflect OA severity and implies a possible role in the pathogenesis of OA.
Muramatsu T. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis.J Biochem. 2002 Sep;132(3):359–71.
Naredo E, Acebes C, Möller I, Canillas F, de Agustín JJ, de Miguel E, et al. Ultrasound validity in the measurement of knee cartilage thickness. Ann Rheum Dis 2009;68:1322–7.
Saarakkala S, Waris P, Waris V, Tarkiainen I, Karvanen E, Aarnio J, et al. Diagnostic performance of knee ultrasonography for detecting degenerative changes of articular cartilage. Osteoarthritis Cartilage 2012;20:376–81.
Disclosure of Interest None declared