HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. The HBO1 inhibitor WM-3835 was utilized to block HBO1 activation. Results: HBO1 mRNA and protein expression is significantly elevated in OS tissues and cells. In established (MG63/U2OS lines) and primary human OS cells, shRNA-mediated HBO1 silencing and CRISPR/Cas9-induced HBO1 knockout were able to potently inhibit cell viability, growth, proliferation, as well as cell migration and invasion. Significant increase of apoptosis was detected in HBO1-silenced/knockout OS cells. Conversely, ectopic HBO1 overexpression promoted OS cell proliferation and migration. We identified ZNF384 (zinc finger protein 384) as a potential transcription factor of HBO1. Increased binding between ZNF384 and HBO1 promoter was detected in OS cell and tissues, whereas ZNF384 silencing via shRNA downregulated HBO1 and produced significant anti-OS cell activity. In vivo , intratumoral injection of HBO1 shRNA lentivirus silenced HBO1 and inhibited OS xenograft growth in mice. Furthermore, growth of HBO1-knockout OS xenografts was significantly slower than the control xenografts. WM-3835, a novel and high-specific small molecule HBO1 inhibitor, was able to potently suppressed OS cell proliferation and migration, and led to apoptosis activation. Furthermore, intraperitoneal injection of a single dose of WM-3835 potently inhibited OS xenograft growth in SCID mice. Conclusion: HBO1 overexpression promotes OS cell growth in vitro and in vivo.

Multimodal imaging probes represent an extraordinary tool for accurate diagnosis of diseases due to the complementary advantages of multiple imaging modalities. The purpose of the work was to fabricate a simple dual-modality MR/CT probe for osteosarcoma visualization in vivo. Protein-directed synthesis methods offer a suitable alternative to MR/CT probe produced by synthetic chemistry. Bovine serum albumin (BSA) bound to gadolinium nanoparticles (GdNPs) was first prepared via a biomimetic synthesis method and was subsequently iodinated by chloramine-T method. The final iodinated BSA-GdNPs (I-BSA-GdNPs) showed excellent chemical stability and biocompatibility, intense X-ray attenuation coefficient, and good MR imaging ability. However, an iodinated protein nanoparticles synthesis for MR/CT imaging, as well as its useful application, has not been reported yet. Intravenous injection of I-BSA-GdNPs into orthotopic osteosarcoma-bearing rats led to its accumulation and retention by the tumor, allowing for a noninvasive tumor dual-modality imaging through the intact thigh. The long-circulating dual-model I-BSA-GdNPs probes possess potential application for image-guided drug delivery and image-guided surgery. Our study is therefore highlighting the properties of albumin in this field combined with its useful use in dual-model MR/CT osteosarcoma visualization, underlining its potential use as a drug carrier for a future therapy on cancer.

No abstract

Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney- Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis.

Abstract. Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling. IntroductionSince the use of biodegradable implants to heal fractures by Rokkanen et al in 1985, the method of using biodegradable materials has been widely applied in orthopedic surgeries (1-3). Biodegradable materials exhibit various advantages in the treatment of fractures compared with the use of traditional metal implants, including the elimination of implant removal, reduction of the 'stress shielding' effect, improvement of biocompatibility, reduction of radiological artifacts and utilization of magnetic resonance imaging assessment following surgery (4,5). Poly-D-L lactide (PDLLA) is a material with an intermediate degradation time (PDLLA begins to degrade at ~12 weeks) and may be completely replaced by bone tissue following surgery, thus, it is considered to be one of the most effective biodegradable materials for the treatment of fractures (6-8). However, with the exception of clinical outcomes, the differences in the biological processes following the use of PDLLA and metal fixation to treat a fracture remain unknown.The fracture healing process has been widely accepted to comprise a series of overlapping phases; these include inflammation, repair and remodeling events (9). This multistage repair process involves a variety of complex and well-orchestrated cellular and molecular processes, and should be considered as a special...

We here showed that ADCK1 (AarF domain-containing kinase 1), a mitochondrial protein, is upregulated in human osteosarcoma (OS) tissues and OS cells. In primary and established OS cells, ADCK1 shRNA or CRISPR/Cas9-induced ADCK1 knockout (KO) remarkably inhibited cell viability, proliferation and migration, and provoked apoptosis activation. Conversely, ectopic ADCK1 overexpression exerted pro-cancerous activity by promoting OS cell proliferation and migration. ADCK1 depletion disrupted mitochondrial functions in OS cells and induced mitochondrial membrane potential reduction, ATP depletion, reactive oxygen species production. Significantly, ADCK1 silencing augmented doxorubicin-induced apoptosis in primary OS cells. mTOR activation is important for ADCK1 expression in OS cells. The mTOR inhibitors, rapamycin and AZD2014, as well as mTOR shRNA, potently decreased ADCK1 expression in primary OS cells. In nude mice, the growth of subcutaneous pOS-1 xenografts was largely inhibited when bearing ADCK1 shRNA or ADCK1 KO construct. Moreover, ADCK1 KO largely inhibited pOS-1 xenograft in situ growth in proximal tibia of nude mice. ADCK1 depletion, apoptosis activation and ATP reduction were detected in pOS-1 xenografts bearing ADCK1 shRNA or ADCK1 KO construct. Together, the mitochondrial protein ADCK1 is required for OS cell growth and is a novel therapeutic target of OS.

Objective To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. Methods Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27‐67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS‐ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS‐ADL were obtained. Randomized controlled trials were used in this study for analysis. Results All patients were followed up with average time of 9.3 months(3‐29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post‐operation, patients in the interportal group, the mHHS and HOS‐ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre‐operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post‐operation (P < 0.05); Patients in the periportal group, the mHHS and HOS‐ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre‐operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post‐operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. Conclusion Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow‐up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule.