Growth factors are reported to play an important role in healing after acute Achilles tendon rupture (ATR). However, the association between growth factors and patient outcome has not been investigated previously. The aim of this retrospective study is to identify growth factors and related proteins which can be used as predictors of healing after ATR, ethical approval was obtained from the Regional Ethical Review Committees in Sweden and followed the guidelines of the Declaration of Helsinki. The study included 28 surgically treated patients (mean age 39.11 ± 8.38 yrs) with acute ATR. Healing was assessed by microdialysate two weeks after the surgery and performed on both injured and contralateral un-injured leg. The microdialysates were analyzed by proteomics based on mass spectrometry (MS) to detect growth factor expressions in ATR patients. One year after the surgery, healing outcomes were evaluated by patient-reported Achilles tendon Total Rupture Score (ATRS), Foot and Ankle Outcome Score (FAOS), and functional outcomes by heel-rise test. A total of 1549 proteins were detected in the microdialysates of which 20 growth factor/ related proteins were identified. 7 of these were significantly up-regulated (IGFBP2, Fold change (FC) = 4.07, P = 0.0036; IGFBP4, FC = 3.06, P = 0.009; CTGF, FC = 15.83, P = 0.003; HDGF, FC = 4.58, P = 0.003; GRB2, FC = 14.8, P = 0.0004; LTBP1, FC = 12.08, P = 0.0008;
Articular cartilage is a relatively hypoxic tissue with a unique extracellular matrix that is enriched with cations, resulting in an elevated interstitial fluid osmolarity. Several biomechanical and physicochemical stimuli are reported to influence chondrocyte metabolism. For regenerative in vitro applications, increasing the extracellular osmolarity above plasma level to more physiological valuesinduces chondrogenic marker expression and the differentiation of chondroprogenitor cells. Calcineurin inhibitor FK506 modulates the differentiation of primary chondrocytes under such conditions and its effect on cell proliferation, extracellular matrix quality, and BMP- and TGF-β signaling will be described. Supraphysiological osmolarity compromises chondrocyte proliferation, while physosmolarity or FK506 did not. Rather, the combination of the latter increased proteoglycan and collagen expression in chondrocytesin vitro and in situ, affecting expression of TGF-β-inducible protein