The accelerated effect of recombinant human bone morphogenetic protein 2 delivered by ß-tricalcium phosphate on tendon-to-bone repair process in rabbit models.

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) plays an important role in the tendon-to-bone repair process. However, there is no previous literature on acceleration of the tendon-to-bone repair process by BMP-2 delivered by ß-tricalcium phosphate (ß-TCP). The aim of this study was to investigate the accelerated effect of recombinant human BMP-2 (rhBMP-2) delivered by ß-TCP on the tendon-to-bone repair process. METHODS: The infraspinatus tendon of elderly female Japanese white rabbits was detached from its insertion site on the humerus. A bone tunnel (4.2 mm) was created at the original insertion site of the tendon, which was repaired using the McLaughlin procedure after filling in ß-TCP (porosity 75%) without BMP-2 (control group) or with 10 µg rhBMP-2 (BMP group). The rabbits were sacrificed at the second, fourth, and eighth weeks after surgery for histologic analysis and biomechanical testing. We also evaluated the maturity of the tendon-to-bone junction using the tendon-to-bone maturity score. RESULTS: Histologic analysis revealed no significant difference between the groups at 2 and 8 weeks but a more abundant organized fibrocartilage at the tendon-to-bone junction in the BMP group at 4 weeks. The tendon-to-bone maturity score improved sequentially. The interface of the BMP group at 4 weeks had significantly improved biomechanical properties than that of the control group. CONCLUSION: The tendon-to-bone repair process was facilitated by the use of rhBMP-2 delivered by ß-TCP at 4 weeks.

Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression.

Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1ΔLimb/ΔLimb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1, which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.

Knowledge of pharmacy students about doping, and the need for doping education: a questionnaire survey.

BACKGROUND: Anti-doping activities are carried out on a global scale. Based on these activities, the specialty of "sports pharmacist," which entails a deeper comprehension of doping, use of supplements, and appropriate drug use for athletes, was established in 2009 in Japan. It is difficult to say whether the education on doping is adequate for pharmacy students who will be eligible to become sports pharmacists. It is also unclear how well these students understand doping. Therefore, the aim of this study was to investigate pharmacy students' current knowledge of appropriate drug use, doping and use of supplements, and to explore the need for further education on these topics. METHODS: A questionnaire survey was conducted from July 3rd to August 2nd in 2014 at Showa University in Japan. A total of 406 respondents (2nd- to 6th-year students) were assessed as eligible. Group comparison was used to compare those who had attended a lecture about doping and those who had not. RESULTS: Most of the students only knew the word doping and had not attended a lecture on the subject, but 72% of them expressed a desire to attend one. Over half did not know that the most common doping violation in Japan is unintentional doping, and were unfamiliar with certain past cases of doping. In addition, 41% did not know that over-the-counter medicines and dietary supplements might contain prohibited substances, and 87% were unaware that names of prohibited substances might not appear on the ingredient labels of dietary supplements. In contrast, attending a lecture on doping was effective in facilitating the acquisition of all these types of knowledge. CONCLUSIONS: It is important to provide more opportunities for appropriate education of pharmacy students on the topic of doping, given that interest exists and attending a lecture on the topic appears to be useful. More education about doping for pharmacy students would be as effective for anti-doping activities as is education of athletes.

Local co-application of zoledronate promotes long-term maintenance of newly formed bone induced by recombinant human bone morphogenetic protein 2.

Bone Morphogenetic Proteins (BMPs) strongly induce the recruitment and differentiation of mesenchymal progenitor cells into mature osteoblasts, but also directly and indirectly stimulate differentiation of osteoclast progenitor cells and acceleration of mature osteoclasts function leading excessive bone resorption. Bisphosphonates, such as zoledronate (ZOL), inhibit osteoclasts function and osteoclasts mediated bone resorption. The short or middle term effect of BMPs and bisphosphonates on bone formation were previously reported, but there was no study that argue about the long term effect of bisphosphonates on BMP-induced bone anabolism. The present study demonstrated that the local administration of ZOL with recombinant human BMP-2 (rh-BMP-2) using beta tricalcium phosphate (ß-TCP) as a carrier had superior efficacy not only to augment the BMP-induced new ectopic bone formation but to maintain the trabecular bone structure inside the new bone for long period. Histological analysis showed that rh-BMP-2/ß-TCP composite induced trabecular bone resorption especially inside the new bone nodules over time, whereas no trabecular bone resorption was seen in rh-BMP-2/ZOL/ß-TCP composite reducing the number of TRAP-positive cells. Thus, inhibition of bone resorption by bisphosphonate, such as ZOL, would be one of the advantageous ways to augment the new bone formation induced by rh-BMP-2, and moreover local co-application of ZOL using ß-TCP as a carrier can be a useful material for long term suppression of osteoclastic resorption and thereby maintain the structure of new bone formation induced by rh-BMP-2.

[Compartment syndrome in bilateral lower legs after total cystectomy: a case report].

We report a case of compartment syndrome in bilateral lower legs after total cystectomy with urethrectomy and ileal conduit diversion. A 64-year-old man who had diabetes mellitus for 20 years underwent an operation for invasive bladder cancer. He was placed in the lithotomy position and both lower legs were protected with an elastic stocking and intermittent pneumatic compression for prevention of deep vein thrombosis during the operation. Seven hours postoperatively, he complained of bilateral calf pain. Eleven hours postoperatively, skin redness, swelling, movement and sensory disorder of bilateral lower legs were found. Contrasting computed tomography (CT) of lower legs showed the swelling of bilateral soleus muscles and gastrocnemius muscles without any contrasting effect. Creatinine phosphokinase (CPK) increased to 46, 740 IU/l and the intramuscular pressure was 50 mmHg. He was diagnosed with compartment syndrome, in bilateral lower legs and emergent fasciotomy was performed. Bilateral calf pain was improved immediately after fasciotomy and could walk on his own after rehabilitation. Lower leg compartment syndrome is an uncommon disease but may require lower leg amputation or result in death if the treatment is delayed. Urologists should recognize this disease as a complication after prolonged operation in the lithotomy position.