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.

Aims

Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown.

The purpose of this study was to analyze the long-term effect of arterial perfusion of drugs and bone marrow stromal cells (bMSCs) on osteonecrosis of femoral head (ONFH). From Jan 1997 to Mar 2004, one hundred and seventeen patients with ONFH were consecutively enrolled to receive a digital subtraction angiography (DSA) in arteriae circumflexa femoris medialis and arteriae circumflexa femoris lateralis. In DSA, a dosage of drugs (urokinase, salvia injection, and tetramethylpyrazine) and autologous bMSCs or only the drugs were perfused into the arteries. The morphological changes of the arteries in DSA after perfusion were recorded. Symptoms radiographs, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at one month, six months, one year, 2 years and 5 years after the treatment. 83 patients were followed up for more than five years. The median follow-up period was 7.9 years.

After the drugs had been perfuse, the arteries became thicker, and more than 2 branches appeared in DSA. Five years after the operation, the Harris hip score of 32 patients (38 hips) treated by arterial perfusion of simplex drugs (group A) increased from 59.24±5.28 to 71.80±6.37 (p< 0.01), and the excellent and good rate of centesimal evaluation was 57.9%. The Harris hip score of 51 patients (59 hips) treated by arterial perfusion of drugs and autologous bMSCs (group B) increased from 59.52±4.85 to 78.29±6.05 (p< 0.01), and the excellent and good rate was 78.0% which was significantly higher than that of group A (p=0.035). Since two years after operation, the Harris hip score of group A was significantly higher than that of group B (p< 0.01).

Among the patients in group B, the rate of excellent and good in early stages (˜,˜ a and ˜ b according to Ficat classifying, 50 hips) was 84.0%, which was better than the rate in the terminal stage (Ficat III, 9 hips, the excellent and good rate was 44.4%)(p = 0.028), and the rate of excellent and good in low age group (< 40 years, 33 hips) was also better than that in high age group (≥ 40 years, 26 hips)(p=0.038).

We conclude that arterial perfusion of drugs and autologous bMSCs treating osteonecrosis of femoral head is safe and effective. The long-term therapeutic effect is more satisfactory than that of simplex arterial perfusion of drugs.

The purpose is to observe the clinical effects of sodium hyaluronate injection plus herbal fumigation in the treatment of knee osteoarthritis.

58 patients(73knees)were treated by sodium hyaluronate injection plus herbal fumigation with a treatment course of five weeks and after a fellow-up of 6–36 months, the average fellow-up time was 12.1 months, the curative effect showed that 39 patients was excellent (52knees), 11 patients was fine (15knees), 4 patients was midst (5knees), 1 patient was bad (1knees), and the total fineness rate was 91.78%.

Sodium hyaluronate injection plus herbal fumigation in the treatment of early metaphase of knee osteoarthritis, which had a better curative effect, less adverse reaction, and worth to extend clinical application.

To investigate the effect of bilateral total hip replacement for patients with ankylosed hip joints caused by late ankylosing spondylitis (AS) and to discuss its related pre- and post-operation rehabilitation problems.

Data of 20 patients with ankylosed hip joints caused by late AS undergone total hip replacement (40 hips) were reviewed. Among the total 14 patients (28 hips) undergone bilateral total hip replacement, other 6 patients (12 hips) undergone twice operations. We used Harris score, assessment of the joint pain, range of motion to make sure the curative effect of the operative strategy.

The mean duration of follow-up was 3. 8 years, all hip joints function was improved, and the flexion deformity of the involved hips were disappeared. The range of hip flexion were 75°–105°(average 86. 2°), and the range of hip extension were 5°–15°(average 8. 7°), the average Harris score was from 32.8 pre-operation improved to 88.2 post-operation, the patients experienced no pain on their hips, the pain of the knee and the lower back complained before the treatment were obviously relieved.

Bilateral total hip replacement is an effective treatment for ankylosed hip joint caused by late ankylosing spondylitis, early rehabilitation intervention is useful for the functional recovery of the joints

Bipolar Hemiarthroplasty Using Non-cemented Femoral Stem in Non-traumatic Osteonecrosis of the Femoral Head Nine to Nineteen years Follow-up