Wm Ng

Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro

The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.

Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells

To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and tissue engineering.

Soft-Tissue Loop for Medial Patellofemoral Ligament Reconstruction

A patient with patellar instability frequently presents with anterior knee pain, patellar subluxation, or dislocation. Medial patellofemoral ligament (MPFL) has a key role for normal patella tracking and stability. Reconstruction of the MPFL using a hamstring graft is a commonly used procedure for the treatment of chronic lateral subluxation of patella. Anchor sutures and bony tunnels are used for the patellar attachment of the graft. This can be associated with complications such as patella fracture; besides, it does not produce an anatomical reconstruction for the native MPFL that can alter the direction of tension applied on the patella. To overcome these problems, a soft-tissue loop technique is used for MPFL reconstruction. During this procedure, a semitendinosus graft was passed through the prepatellar extensor retinaculum and secured with sutures. The free ends of the graft were then passed between the second and third layers of the medial patellofemoral retinaculum and fixed to a femoral tunnel on the medial femoral condyle with an interference screw. The desired amount of tension on the graft is achieved under direct vision of patella tracking arthroscopically. We found this method to be relatively safe and fast. It is more anatomical and can avoid the complications during the conventional bony procedures.

Radiological analysis of the medial epicondyle in the adolescent throwing athlete.

INTRODUCTION Injuries to the medial structures of the elbow due to overhead throwing games are well documented. However, variations of medial epicondyles are not well described, especially in athletes with fused medial epicondyles. In this study, we evaluated variations in the medial epicondyle of baseball players who were aged 15-17 years and had fused epicondyles. METHODS In this cross-sectional observational study, 155 skeletally mature baseball players with unilateral medial elbow pain and 310 elbow radiographs were reviewed by two independent reviewers. The medial epicondyles were categorised into three groups: normal, elongated or separated. RESULTS Among the 155 patients, 65 (41.9%) had normal epicondyles, 41 (26.5%) had elongated epicondyles and 49 (31.6%) had separated epicondyles. The medial epicondyle was larger on the dominant arm for 125 (80.6%) patients; the mean surface area on the dominant arm was 222.50 ± 45.77 mm2, while that of the non-dominant arm was 189.14 ± 39.56 mm2 (p < 0.01). Among the three categories of medial epicondyles, separated epicondyles had the largest surface area, followed by elongated and normal epicondyles. CONCLUSION Medial epicondyles in adolescent throwing athletes can be categorised into three different groups according to their shape (normal, elongated and separated). We observed a correlation between the shape and the surface area of the medial epicondyle in adolescent throwing athletes, with separated medial epicondyles having the largest surface area. Further studies and follow-up are needed to determine the prognostic value and clinical significance of these morphological variations.

Use of the Tip-Apex Distance in predicting Dynamic Hip Screw Cut Out in Intertrochanteric Fracture of the Femur in Asian Population

The objective of this study was to assess the rate of screw cut out in elderly patients treated with the dynamic hip screw and the relationship to the Tip Apex Distance (TAD). This is a retrospective radiological evaluation of 100 cases of elderly patients with intertrochanteric fracture treated with dynamic hip screw fixation surgically treated between 1998 and 2002. The incidence of screw cut out was assessed and correlation of risk of cut out with the TAD was assessed. The rate of screw cut out was 9.0% and the average length of time to screw cut out was 3.8 months (range, 1 to 6 months) postoperatively. The incidence of screw cut out increased significantly when the TAD was 20 mm or more. The screw cut out rates were 2.9%, 20.0%, 30.8%, 50% and 100% for TAD of 20-24 mm, 25-29 mm, 30-34 mm, 35-44 mm and > 45 mm respectively. Overall, a TAD of 20mm or more was associated with a statistically significant screw cut out risk in this Malaysian population.

Crossing Suture Technique for the Osteochondral Fractures Repair of Patella

Osteochondral fracture of the patella is a common concomitant injury of the knee, especially in lateral patellar instability, and the importance of early stable fixation with minimal complication and early mobilization should be emphasized. Screws and Kirschner wires both absorbable and nonabsorbable have been the common mode of fixation of these fractures. Nevertheless, these fixation techniques require larger osteochondral fragments and are associated with cartilage abrasion, hardware prominence, synovitis, and foreign body reaction. In contrast, suture fixation can adequately stabilize smaller osteochondral fragments without comminution and prevent some of the possible complications of other techniques of fixation. We created 4 holes in a rectangular pattern on the patella oriented perpendicular to its anteroposterior surface. We used readily available, and affordable, no. 2 Ultrabraid sutures inserted into the holes and looped around the osteochondral fragment, compressing it to the patella. The technique is very simple and is relatively easy to learn. It provides secure fixation and allows early mobilization. And it spares the knee from subsequent surgical procedure for removal of metallic implants.

Correlation between Focal Nodular Low Signal Changes in Hoffa's Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication.

Purpose. This study investigates the association between focal nodular mass with low signal in Hoffas fat pad adjacent to anterior femoral cartilage of the knee (FNMHF) and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA) sagittal and axial images of the B1 and C1 region (described later) of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p = 0.00) between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%). Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

Ipsilateral femoral fracture non-union and delayed union treated by hybrid plate nail fixation and vascularized fibula bone grafting: a case report.

Non-union is a well recognized complication of femoral neck fractures. The decision whether to attempt fracture fixation or to resort to hip replacement is particularly difficult in patients in the borderline age group in whom complex attempts at gaining union may fail and later present a difficult revision. On the other hand the patient may be young enough that arthroplasty best be avoided . Besides, presence of ipsilateral femoral shaft fracture with delayed union in addition to the femoral neck non-union will pose major problems at operation. We share our experience in treating a femoral neck fracture non-union with ipsilateral femoral shaft delayed union in the shaft and in the distal femur in a fifty years old patient. The fracture was treated with an angle blade plate and supracondylar nail supplemented with a free vascularised fibular bone grafting and autologous cancellous graft. There was radiological union at fourth month. At sixth months, the patient was free of pain and able to walk without support. Thus, we would like to suggest that vascularised fibula bone grafting with supracondylar nailing is a viable option for this pattern of fracture. Key Words Vascularized fibular bone graft, neck of femur, femoral shaft fracture, non-union

Femoral Shaft Cortical Pathology associated with longterm Alendronate Therapy: A New Classification.

Abstract There are reported cases of cortical reaction over the tension side of the normal femoral shafts in patients on long term treatment with alendronate, leading to subsequent femoral shaft fractures. We performed a retrospective review of patients with low-energy femoral shaft fracture on alendronate, admitted to our institution during the period 2004 to May 2009. The presence of radiological changes of cortical hypertrophy with or without Looser’s zone over the tension side of the femoral bone (normal limb) was determined and correlated with clinical symptoms. Thirteen patients were identified. Average duration of alendronate use was 6.5 ± 3.3 years (ranges, two to 10 years). These radiological changes were noted in four patients. Average duration of alendronate usage in these four patients was 6.5 ± 2.4 years (ranges, 5 to10 years). Prodromal thigh pain was present in a patient, who had cortical hypertrophy with the presence of a Looser’s zone traversing the cortex on the femoral shaft. One patient had Looser’s zone limited at the lateral hypertrophied cortex without prodromal pain. The interobserver kappa coefficient was 0.96. A femoral radiograph should be performed in all patients who are on long-term alendronate therapy who present with thigh pain. We propose a new grading system based on our observation of the radiological features in these four cases. This new grading of the radiological spectrum of femoral shaft cortical pathology has the potential to stratify the risk of low energy femoral fracture for patients treated with long-term alendronate therapy. Key Words Femur, Cortical Hypertrophy, Looser Zone, Alendronate

Causative Factors for Femoral Pin Track Fractures in Navigated Total Knee Arthroplasty

This retrospective radiographic analysis of 57 patients (62 knees) examined two possible factors involved in pin tract fractures of the femur due to navigated total knee arthroplasty (TKA): the angle of the tracker pin with respect to the lateral femoral cortex, and the distance between the tracker pin and the lateral joint line. Our findings demonstrate a relationship between postoperative pin tract induced stress fractures (3 patients), with pin tract angles exceeding 15°. Pin placement at a site more than 10cm from the lateral joint line, did not show any significant association with risk of fracture. These findings lead to enhanced understanding of the causative factors underlying pin track femoral fractures in TKAs.