Epigenetic Regulation in Chondrogenesis

Epigenetics is an essential mechanism to control gene expression and fundamental cellular processes. DNA methylation in CpG-rich promoters correlates with gene silencing. Histone modification including histone acetylation and deacetylation determines the stability of the chromatin structure. Condensed chromatin (heterochromatin), which has a higher-order histone-DNA structure, prevents the access of transcriptional activators to their target genes. The fundamental unit of eukaryotic chromatin consists of 146 bp of DNA wrapped around a histone octamer. Posttranslational modifications of the histone tail and the chromatin remodeling complex disrupt histone-DNA contacts and induce nucleosome mobilization. Histone acetylation of specific lysine residues in the histone tail plays a crucial role in epigenetic regulation. Histone acetylation is a dynamic process regulated by the antagonistic actions of 2 families of enzymes - the histone acetyltransferases (HATs) and the histone deacetylases (HDACs). The balance between histone acetylation and deacetylation serves as a key epigenetic mechanism for transcription factor-dependent gene expression and the developmental process. We review emerging evidence that DNA methylation, histone acetylation modified by HAT and/or HDAC, and transcription factor-associated molecules contribute to a mechanism that can alter chromatin structure, gene expression, and cellular differentiation during chondrogenesis

Early Rehabilitation with Weight-bearing Standing-shaking-board Exercise in Combination with Electrical Muscle Stimulation after Anterior Cruciate Ligament Reconstruction

The objective of early rehabilitation after anterior cruciate ligament (ACL) reconstruction is to increase the muscle strength of the lower extremities. Closed kinetic chain (CKC) exercise induces co-contraction of the agonist and antagonist muscles. The purpose of this study was to compare the postoperative muscle strength/mass of subjects who performed our new CKC exercise (new rehabilitation group:group N) from week 4, and subjects who received traditional rehabilitation alone (traditional rehabilitation group:group T). The subjects stood on the device and maintained balance. Then, low-frequency stimulation waves were applied to 2 points each in the anterior and posterior region of the injured thigh 3 times a week for 3 months. Measurement of muscle strength was performed 4 times (before the start, and then once a month). Muscle mass was evaluated in CT images of the extensor and flexor muscles of 10 knees (10 subjects) in each group. The injured legs of group N showed significant improvement after one month compared to group T. The cross-sectional area of the extensor muscles of the injured legs tended to a show a greater increase at 3 months in group N. This rehabilitation method makes it possible to contract fast-twitch muscles, which may be a useful for improving extensor muscle strength after ACL reconstruction

Histological Analysis of Failed Cartilage Repair after Marrow Stimulation for the Treatment of Large Cartilage Defect in Medial Compartmental Osteoarthritis of the Knee

Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoarthritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin O staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects

Radiographic Prediction of the Results of Long-term Treatment with the Pavlik Harness for Developmental Dislocation of the Hip

In 1957, Pavlik introduced the Pavlik harness as a useful treatment for developmental dislocation of the hip (DDH), and subsequent studies have documented favorable outcomes among patients treated with this device. However, there are only a few articles reporting how early radiographic measurements can be used to determine the prognosis after treatment with the Pavlik harness. In this study, 217 hips from 192 patients whose DDH treatment with the Pavlik harness was initiated before they were 6 months old and whose follow-up lasted at least 14 years (rate, 63.8%) were analyzed using measurements from radiographs taken immediately before and after harness treatment, and at 1, 2, and 3 years of age. Severin's classification at the final follow-up was I or II in 71.9% and III or IV in 28.1% of the hips, respectively. Avascular necrosis of the femoral head (AVN) was seen in 10% of the hips. Stepwise multiple regression analysis was performed to retrospectively determine whether any radiographic factors were related to the final classification as Severin I/II or III/IV. Receiver opera-ting characteristic (ROC) curves were drawn for these factors, and a Wiberg OE angle (Point O was the middle point of the proximal metaphyseal border of the femur) of 2 degrees on the 3-year radiographs was found to be the most useful screening value for judging the acetabular development of DDH cases after treatment with a Pavlik harness, with a sensitivity of 71% a specificity of 93%, and a likelihood ratio of 10.1.</p

Posterior cervical spine arthrodesis with laminar screws: a report of two cases

We performed fixation using laminar screws in 2 patients in whom lateral mass screws, pedicle screws or transarticular screws could not be inserted. One was a 56-year-old woman who had anterior atlantoaxial subluxation (AAS). When a guide wire was inserted using an imaging guide, the hole bled massively. We thought the re-insertion of a guide wire or screw would thus increase the risk of vascular injury, so we used laminar screws. The other case was an 18-year-old man who had a hangman fracture. Preoperative magnetic resonance angiography showed occlusion of the left vertebral artery. A laminar screw was inserted into the patent side (i.e., the right side of C2). Cervical pedicle screws are the most biomechanically stable screws. However, their use carries a high risk of neurovascular complications during screw insertion, because the cervical pedicle is small and is adjacent laterally to the vertebral artery, medially to the spinal cord, and vertically to the nerve roots. Lateral mass screws are also reported to involve a risk of neurovascular injuries. The laminar screw method was thus thought to be useful, since arterial injuries could thus be avoided and it could also be used as a salvage modality for the previous misinsertion.</p

Biomechanical Evaluation of the Fixation Methods for Transcondylar Fracture of the Humerus:ONI Plate Versus Conventional Plates and Screws

We biomechanically evaluated the bone fixation rigidity of an ONI plate (Group I) during fixation of experimentally created transcondylar humerus fractures in cadaveric elbows, which are the most frequently observed humeral fractures in the elderly, and compared it with the rigidity achieved by 3 conventional fixation methods:an LCP reconstruction plate 3.5 using a locking mechanism (Group II), a conventional reconstruction plate 3.5 (CRP) with a cannulated cancellous screw (Group III), and a CRP with 2 cannulated cancellous screws (CS) in a crisscross orientation (Group IV). In the axial loading test, the mean failure loads were:Group I, 98.9+/-32.6;Group II, 108.5+/-27.2;Group III, 50.0+/-7.5;and Group IV, 34.5+/-12.2 (N). Group I fixations failed at a significantly higher load than those of Groups III and IV (p0.05). In the extension loading test, the mean failure loads were:Group I, 34.0+/-12.4;Group II, 51.0+/-14.8;Group III, 19.3+/-6.0;and Group IV, 14.7+/-3.1 (N). Group IV fixations showed a significantly lower failure load than those of Group I (p0.05). The fixation rigidities against mechanical loading by the ONI plate and LCP plate were comparable. These results suggested that an ONI system might be superior to the CRP and CS method, and comparable to the LCP method in terms of fixation rigidity for distal humerus fractures.</p