TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis.

PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks.

PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A.

Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA.

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration.

A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China.

The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).

we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation.

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; TGFBI, FC = 5.54, P = 0.001) and 1 down-regulated (IGFBP6) in the injured compared to the contralateral healthy side. Linear regression analysis revealed that TGFB1 was positively associated with improved ATRS (r = 0.585, P = 0.04) as well to ATRS subscales: less limitation in running (r = 0.72, P = 0.004), less jumping limitation (r = 0.764, P = 0.001) and less limitation caused by decreased tendon strength (r = 0.665, P = 0.012). Interestingly, all 7 up-regulated proteins were positively associated with less jumping limitations (IGFBP2, r = 0.667, P = 0.015; IGFBP4, r = 0.675, P = 0.013; CTGF, r = 0.668, P = 0.015; HDGF, r = 0.672, P = 0.014; GRB2, r = 0.665, P = 0.016; LTBP1, r = 0.663, P = 0,016). No associations were observed among any of the growth factor and FAOS or patient's functional outcomes.

We conclude that growth factors and related proteins play a crucial role in ATR healing. More specifically, TGFB1 may be used as prognostic biomarker of the patient-reported outcome 1-year post-surgery. These results may be used to develop more specific treatments to improve ATR healing.

Introduction

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy affecting approximately 3 million people in China (Stone R, 2009). The precise aetiology of KBD is not clear, but the lack of selenium and the pollution of mycotoxins in food are a suspected cause of KBD. In this pilot study, we use a rat model to investigate the effect of low selenium and T-2 toxin on articular cartilage metabolism.