Controlled Release of TGF-ß3 for Effective Local Endogenous Repair in IDD Using Rat Model.

Introduction: Intervertebral disc (IVD) degeneration (IDD) is one of the most widespread musculoskeletal diseases worldwide and remains an intractable clinical challenge. Currently, regenerative strategies based on biomaterials and biological factors to facilitate IVD repair have been widely explored. However, the harsh microenvironment, such as increased ROS and acidity, of the degenerative region impedes the efficiency of IVD repair. Here, an intelligent biodegradable nanoplatform using hollow manganese dioxide (H-MnO2) was developed to modulate the degenerative microenvironment and release transforming growth factor beta-3 (TGF-ß3), which may achieve good long-term therapeutic effects on needle puncture-induced IDD. Methods: Surface morphology and elemental analysis of the MnO2 nanoparticles (NPs) were performed by transmission electron microscopy and an energy-dispersive X-ray spectroscopy detector system, respectively. The biological effects of MnO2 loaded with TGF-ß3 (TGF-ß3/MnO2) on nucleus pulposus cells (NPCs) were assessed via cytoskeleton staining, EdU staining, qPCR and immunofluorescence. The efficacy of TGF-ß3/MnO2 on needle puncture-induced IDD was further examined using MRI and histopathological and immunohistochemical staining. Results: The MnO2 NPs had a spherical morphology and hollow structure that dissociated in the setting of a low pH and H2O2 to release loaded TGF-ß3 molecules. In the oxidative stress environment, TGF-ß3/MnO2 was superior to TGF-ß3 and MnO2 NPs in the suppression of H2O2-induced matrix degradation, ROS, and apoptosis in NPCs. When injected into the IVDs of a rat IDD model, TGF-ß3/MnO2 was able to prevent the degeneration and promote self-regeneration. Conclusion: Use of an MnO2 nanoplatform for biological factors release to regulate the IDD microenvironment and promote endogenous repair may be an effective approach for treating IDD.

Curettage through a wide cortical window for treatment of a primary aneurysmal bone cyst of the patella.

A 27-year-old man presented with intermittent right knee pain for 1 year with no previous trauma. Physical examination revealed only tenderness over the patella. Typical fluid-fluid levels were visible on magnetic resonance imaging (MRI), which highly suggested aneurysmal bone cyst (ABC) of the patella. After removal of a large window of thin cortical bone, curettage and bone grafting followed by cerclage wiring was performed. Histology confirmed the initial diagnosis of primary ABC of the patella. At the final follow-up visit at 71 months after surgery, the patient had normal joint activity with no pain or evidence of recurrence. Previous publications indicated patellectomy in the initial series, but curettage and bone grafting have more recently provided excellent results and good graft incorporation in most cases, even for aggressive lesions. In our patient, thorough curettage and bone grafting through a wide cortical window followed by cerclage wiring fixation and figure-eight sutures was a successful treatment option for primary ABC of the patella without articular disruption.

[The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair].

Objective: To investigate the role and mechanism of S100 calcium binding protein B (S100B) in osteoarthritis (OA) cartilage damage repair. Methods: Twenty New Zealand rabbits were randomly divided into control group and model group, with 10 rabbits in each group. Rabbits in the model group were injured by the right knee joint immobilization method to make the artilage injury model, while the control group did not deal with any injury. After 4 weeks, the levels of interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in synovial fluid were detected by ELISA method; the mRNA and protein expressions of S100B, fibroblast growth factor 2 (FGF-2), and FGF receptor 1 (FGFR1) in cartilage tissue were examined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot assay. Human synovial fibroblasts (SF) were isolated and cultured in vitro. The effects of S100B overexpression and knockdown on the levels of IL-1ß and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Moreover, the effects of FGFR1 knockdown in above S100 overexpression system on the levels of IL-1ß and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Results: ELISA detection showed that the expressions of IL-1ß and TNF-α in the synovial fluid of the model group were significantly higher than those of the control group ( P<0.05); qRT-PCR and Western blot detection showed that the mRNA and protein expressions of S100B, FGF-2, and FGFR1 in cartilage tissue were significantly higher than those of the control group ( P<0.05). Overexpression and knockdown S100 could respectively significantly increase and decrease lipopolysaccharides (LPS) induced IL-1ß and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05); whereas FGFR1 knockdown could significantly decrease LPS induced IL-1ß and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05). Conclusion: S100B protein can regulate the inflammatory response of SF and may affect the repair of cartilage damage in OA, and the mechanism may be related to the activation of FGF-2/FGFR1 signaling pathway.

S100B regulates inflammatory response during osteoarthritis via fibroblast growth factor receptor 1 signaling.

The present study aimed to investigate the role of S100B in the inflammation process during osteoarthritis (OA). OA cartilage samples were collected for S100B expression analysis. S100B expression levels were significantly increased in patients with OA compared with the Controls (1.28±0.66 vs. 0.42±0.31; P=0.01) and were determined to be correlated with TNF­α (r=0.42; P=0.04) and IL­1ß (r=0.73; P=0.001) expression levels. Orthopedic casting tape was used to immobilize the right knee at 180˚ extension of adult female New Zealand white rabbits for 4 weeks to establish an OA model. Cartilage specimens from the medial femoral condyle of these rabbits were used for histological confirmation and immunohistochemical analyses, whereas synovial fluid was used in ELISA assays for tumor necrosis factor (TNF)­α and interleukin (IL)­1ß expression levels. Human synovial fibroblasts from the knee synovial tissues of normal patients with traumatic injury were transfected with S100B overexpression and knockdown plasmids and subjected to lipopolysaccharide (LPS) stimulation; subsequently, TNF­α and IL­1ß expression levels in conditioned medium were determined by ELISA; S100B overexpression and knockdown significantly increased and decreased the TNF­α and IL­1ß expression levels, respectively. Increased TNF­α (573.3±15.4 vs. 102.6±8.7 pg) and IL­1ß (378.6±7.2 vs. 170.1±5.8 pg) expression levels were detected in OA model rabbits compared with the Control rabbits. Additionally, S100B, fibroblast growth factor (FGF)­1 and FGF receptor (FGFR)­1 mRNA and protein expression levels were increased in OA model rabbits compared with the Control group. FGFR1 knockdown significantly decreased TNF­α and IL­1ß expression levels in LPS­stimulated S100B­overexpressing human synovial fibroblasts. S100B is involved in FGFR1 signaling­mediated inflammatory response during OA, which may be considered as a potential therapeutic target.

Clinical efficacy of meniscus plasty under arthroscopy in middle-aged and elderly patients with meniscus injury.

Clinical efficacy of meniscal plasty and total meniscectomy under arthroscopy in treating middle-aged and elderly patients with meniscus injury were explored. One hundred and fifteen elderly patients with meniscal injuries treated in the First Peoples Hospital of Wujiang District Suzhou from May 2012 to October 2014 were retrospectively analyzed. They were randomly divided into meniscal plasty group (experimental group) and total meniscectomy group (control group). Length of stay, operation time and VAS between the two groups were compared. Knee function was evaluated before the surgery and at the final follow-up using IKDC 2000 and Lysholm score. The differences of postoperative clinical efficacy and complications in both groups were observed. Postoperative IKDC 2000 and Lysholm score in the experimental group were superior to those of control group (P<0.001). There was no significant difference in the relieving effect of knee pain between the two types of procedures (P>0.05). Shorter operation time was found in control than that of experimental group. We did not observe remarkable differences in length of stay and postoperative complication rate between the two groups (P>0.05). Both meniscal plasty and total meniscectomy under arthroscopy can effectively relieve knee pain in a short time. Meniscal plasty could remarkably alleviate the progression of knee osteoarthritis, maintain knee function and improve daily life of affected population. We considered that meniscal plasty should be served as the preferred approach in treating middle-aged and elderly patients with meniscus injury.

Application value of expansive pedicle screw in the lumbar short-segment fixation and fusion for osteoporosis patients.

Clinical value of expansive pedicle screw in lumbar short-segment fixation and fusion for patients with osteoporosis was investigated. A total of 80 patients with lumbar compression fracture but without obvious nerve compression were selected and divided into the observation group (n=40) and the control group (n=40) using a random number table. The observation group used the expansive pedicle screw, and the control group received conventional pedicle screw fixation and bone graft fusion. In the observation group, the operation and hospitalization time after operation were shorter and the intraoperative bleeding amount was less than that in control group (p<0.05). At 1 week, 1, 3 and 6 months after operation, the observation group had better straight leg raising test (SLRT) scores, higher lower limb sensory scores but lower visual analogue scale (VAS) scores than control group (p<0.05). Besides, the proportions of postoperative infection, dural mater tear, nerve root injury and spinal cord injury during operation in the observation group were lower than those in the control group (p<0.05), and the bone graft fusion rates at 3 and 6 months after operation were obviously superior to those in control group (p<0.05). Moreover, after operation, the spinal stenosis rate in the observation group was lower than that in control group (p<0.05), the vertebral height ratio was larger than that in control group (p<0.05), and the Cobb's angle was smaller than that in the control group (p<0.05). In addition, there was a negative correlation between bone mineral density (BMD) and hospitalization time after operation in the observation group (p<0.05). In conclusion, the internal fixation with expansive pedicle screw for osteoporosis patients with lumbar compression fracture is characterized by short operation time, less intraoperative bleeding, few complications, quick recovery of postoperative neurological function and satisfactory surgical effect. However, reasonable intervention in osteoporosis is also necessary.

Amplified HMGA2 promotes cell growth by regulating Akt pathway in AML.

PURPOSE: The aim of this study was to investigate how the amplification of HMGA2 contributes to acute myeloid leukemia (AML) cell proliferation. METHODS: The amplification and expression of HMGA2 were examined by FISH, qRT-PCR and Western blot in AML cases. The effect of HMGA2 knockdown on cell proliferation was analyzed with XTT, colony-forming assays and BrdUrd incorporation assays. The effects of HMGA2 knockdown on cell cycle were studied by flow cytometry analysis. The progression of AML cells in vivo was examined by the xenografted tumor model. The interaction between Akt pathway and HMGA2 was examined by Western blot. RESULTS: HMGA2 is amplified in AML, and the levels of HMGA2 messenger RNA (mRNA) and protein expressed in AML cells were significantly higher than those in normal cells, which may be related to NR and prognosis of AML patients. Reduction in HMGA2 expression in AML cells inhibited cell proliferation through a decrease in the protein expression of pAkt and pmTOR, compared with control cells. CONCLUSIONS: HMGA2 is predominantly amplified and expressed in AML cells, and that aberrant expression of HMGA2 induces AML cell proliferation through the PI3K/Akt/mTOR signaling pathway. Inhibition of HMGA2 expression represents an attractive target for AML therapy.