The role of transcriptional factor brachyury in the development and repair of nucleus pulposus

Transcription factor Brachyury,a protein containing 435 amino acids,has been widely investigated and reported in notochord differentiation and nucleus pulposus development.The crucial functions and underlying mechanisms by Brachyury are discussed in this paper,which suggests Brachyury can be developed into a potential novel target for the therapy of intervertebral disc degeneration.

Fibrosis of the Quadriceps Muscles Secondary to Sickle Cell Disease: A Case Report

The musculo-skeletal system is commonly affected in sickle cell disease, manifesting itself as bone infarction, femoral head osteonecrosis, osteomyelitis, myonecrosis, myofibrosis and fascitis. Myositis and fasciitis are observed during a vaso-occlusive crisis in 4% of patients. Pain and swelling of bilateral proximal groups of muscles of upper and lower limbs are common presenting complaints due to prolonged sickling crises [1]. We report a case of 30-year old known HbSS patient with bilateral knee stiffness of two months duration, with associated swelling and warmth of both thighs. No preceding history of trauma. He was said to suffer at least two sickling crises in a month with the last one occurring one week prior to presentation. X-ray of the thigh showed no calcification in muscle groups. He was commenced on flexion-extension exercises.

Return to physical activity after gastrocnemius recession

AIM To prospectively investigate the time taken and patients' ability to resume preoperative level of physical activity after gastrocnemius recession. METHODS Endoscopic gastrocnemius recession(EGR) was performed on 48 feet in 46 consecutive sportspersons, with a minimum follow-up of 24 mo. The Halasi Ankle Activity Score was used to quantify the level of physical activity. Time taken to return to work and physical activity was recorded. Functional outcomes were evaluated using the short form 36(SF-36), American Orthopedic Foot and Ankle Society(AOFAS) Hindfoot score and modified Olerud and Molander(O and M) scores respectively. Patient's satisfaction and pain experienced were assessed using a modified Likert scale and visual analogue scales. P-value < 0.05 was considered statistically significant.RESULTS Ninety-one percent(n = 42) of all patients returned to their preoperative level of physical activity after EGR. The mean time for return to physical activity was 7.5(2-24) mo. Ninety-eight percent(n = 45) of all patients were able to return to their preoperative employment status, with a mean time of 3.6(1-12) mo. Ninety-six percent(n = 23) of all patients with an activity score > 2 were able to resume their preoperative level of physical activity in mean time of 8.8 mo, as compared to 86%(n = 19) of patients whose activity score was ≤ 2, with mean time of 6.1 mo. Significant improvements were noted in SF-36, AOFAS hindfoot and modified O and M scores. Ninety percent of all patients rated good or very good outcomes on the Likert scale.CONCLUSION The majority of patients were able to return to their pre-operative level of sporting activity after EGR.

Combined use of extensively porous coated femoral components with onlay cortical strut allografts in revision of Vancouver B2 and B3 periprosthetic femoral fractures

Background Periprosthetic femoral fractures following total hip arthroplasty are getting more prevalent. The aim of this study was to evaluate the clinical results of combined use of uncemented extensively porous coated femoral components with onlay cortical strut allografts in revision of Vancouver type B2 and B3 periprosthetic femoral fractures. Methods Thirteen hips after total hip arthroplasty in 13 patients who suffered a Vancouver B2 or B3 periprosthetic fracture were treated with an uncemented extensively porous coated femoral component combined with onlay cortical strut allografts. Each patient was assigned a Harris hip score, and a visual analog scale （VAS） score for pain and satisfaction. Radiographs were examined for component stability, fracture site and allograft-host union and allograft reconstruction. Results At an average of 5.3-year follow-up, no patient required repeat revision. The average Harris hip score was （71.8±6.3） points, the pain VAS score was （16.6±4.3） points, and the patient satisfaction VAS score was （81.5±5.7） points Radiographic examination showed no detectable loosening of the prostheses, and 12 cases were presented fixation by osseointegration and the other one was stable fibrous ingrown fixation. All fractures united for （5.2±1.4） months in average. And all onlay strut allografts united to host bone for about （11.5±2.6） months. Conclusions Combined use of uncemented, long stemmed, extensively porous coated implant with cortical onlay strut allografts can achieve good clinic results and high rate of union for both fracture site and allograft-host bone junction. This technique could be used routinely to augment fixation and healing of Vancouver B2 and B3 periprosthetic fractures.

RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss

The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis,whereas nuclear accumulation ofβ-catenin requires the activation of Rac1,a member of the Rho small GTPase family.The aim of the present study was to investigate the role of RhoA/Rho kinase(Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss.We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3βat Tyr216,resulting in Gsk3βactivation and subsequentβ-catenin destabilization.In line with these molecular events,RhoA loss-or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion ofβ-catenin,respectively.Likewise,RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it.Importantly,high RhoA/Rock activity closely correlates with Jak and Gsk3βactivities but inversely correlates withβ-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice,whereas systemic inhibition of Rock therefore activates theβ-catenin signaling to antagonize aging-associated bone loss.Taken together,these results identify RhoA/Rock-dependent Gsk3βactivation and subsequentβ-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.