FoxO3 Regulates Mouse Bone Mesenchymal Stem Cell Fate and Bone-Fat Balance During Skeletal Aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-polymerase chain reaction, Western blot, and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling, respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs and is a potential target for the prevention of age-related osteoporosis.

A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis.

Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral-biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)-based nanoparticles (NPs) are integrated into poly(D, L-lactide)-poly(ethylene glycol)-poly(D, L-lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self-assembled ChS and ε-poly-l-lysine (EPL) NPs are prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in interleukin-1ß (IL-1ß)-mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS-based hydrogel system offers a potential strategy to regulate the chondrocyte-macrophage crosstalk, thus re-establishing the anti-inflammatory and immunomodulatory microenvironment for OA therapy.

Comparison of Hidden Blood Loss Between Three Different Surgical Approaches for Treatment of Thoracolumbar Fracture.

Purpose: To examine the hidden blood loss (HBL) in treatment of AO type A1-A3 thoracolumbar fractures with three different approaches and to explore the influential factors of HBL among patients after the surgery of internal fixation for thoracolumbar fractures. Methods: We retrospectively studied 85 patients in treatment of thoracolumbar fractures: 25 patients via percutaneous approach (Group A), 33 patients via paraspinal approach (Group B), and 27 patients via conventional open approach (Group C). The demographic information of the patients was collected. Each patient's preoperative and postoperative hematocrit were recorded and used for calculating the blood loss according to the Gross's formula. The difference of blood loss between the three groups was measured by ANOVA. And influential factors were further analyzed by multivariate linear regression analysis in each group. Results: The average HBL was 240.0 ± 65.1 mL in Group A, 313.7 ± 138.1 mL in Group B, and 382 ± 153.8 mL in Group C. There was statistical difference in the HBL between three groups (P = 0.000). However, multivariate linear regression analysis revealed that HBL of three approaches was not associated with age, gender, body mass index (BMI), percentage of height loss, percentage of height restoration, fracture type, or operation time. Conclusion: There was a substantial HBL in the treatment of thoracolumbar fractures, which was neglected by surgeons. Further investigation is necessary to study the risk factors for surgery on HBL in treatment of thoracolumbar fractures.

The Role of Unilateral Balloon Kyphoplasty for the Treatment of Patients with OVCFS: A Systematic Review and Meta-Analysis.

BACKGROUND: An increasing number of studies have been conducted to apply unilateral balloon kyphoplasty in the treatment of ostroporotic vertebral compression fractures (OVCFs). However, the efficacy and safety of unilateral kyphoplasty and whether a unilateral or a bilateral approach is superior is controversial. OBJECTIVES: The purpose of this study was to evaluate the role of unilateral balloon kyphoplasty and use meta-analysis to compare the efficacy and safety of unilateral and bilateral kyphoplasty in patients with OVCFs. STUDY DESIGN: A systematic literature search was conducted from 1970 to April 2017 using Medline database and the Cochrane Central Register of Controlled Trials. Articles were limited to those published in English. Randomized controlled trials and nonrandomized comparative studies were also included. SETTING: The following search terms were used: "osteoporotic vertebral compression fractures," or "OVCF," and "unilateral kyphoplasty," or "unipedicular approach," or "single balloon kyphoplasty," or "one balloon kyphoplasty." A comprehensive search of reference lists of retrieved articles and previous published reviews was also performed to ensure inclusion of all possible studies. METHODS: All potential articles were independently reviewed by 2 investigators for inclusion into the final analysis. MINORS score was used for nonrandomized studies, and Detsky quality index was applied for prospective randomized controlled trials. Systematic review and meta-analysis was performed for the included studies. RESULTS: After unilateral balloon kyphoplasty the mean postoperative visual analog score (VAS) was from 1.74 to 4.77, mean postoperative kyphotic angle was from 5.9º to 11.22º, and complications involving cement leaks was from 6.8 to 21.9% or adjacent level fractures was from 0 to 5.6%). Unilateral kyphoplasty had significantly lower operative time, and less bone cement volume; however, the postoperative VAS, Oswestry Disability Index (ODI), vertebral height restoration rate, and cement leakage and adjacent vertebral fracture rate, were similar to bilateral kyphoplasty. LIMITATIONS: Only 6 randomized controlled trials and 3 retrospective comparative studies were selected for analysis. Heterogeneity was detected among the studies when we pooled the outcomes. CONCLUSIONS: Based on the available evidence, the clinical and radiological results of unilateral balloon kyphoplasty were as good as those of bilateral balloon kyphoplasty for the treatment of OVCFs. And unilateral kyphoplasty had advantages in terms of operation time, radiation exposure, and cost. KEY WORDS: Unilateral balloon kyphoplasty, bilateral balloon kyphoplasty, osteoporotic vertebral compression fractures, complications of balloon kyphoplasty, meta-analysis.

Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling.

Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Treatment of human umbilical vein endothelial cells (HUVECs) with ASA VI (20-80 µg/mL) dose-dependently promoted the proliferation, migration and enhanced their angiogenic ability in vitro, which were associated with the up-regulated HIF-1α/VEGF signaling. Full-thickness cutaneous wound model rats were injected with ASA VI (20 mg·kg-1·d-1, iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound healing, and more blood vessels were observed in the regenerated tissue. Due to rapid vascularization, the cellular proliferation status, granulation tissue formation, collagen matrix deposition and remodeling processes were all accelerated, resulting in efficient wound healing. In summary, ASA VI promotes angiogenesis of HUVECs in vitro via up-regulating the HIF-1α/VEGF pathway, and efficiently enhances the vascularization in regenerated tissue and facilitates wound healing in vivo. The results reveal that ASA VI is a potential therapeutic for vessel injury-related wounds.

Efficacy of Using Intermediate Screws in Short-Segment Fixation for Thoracolumbar Fractures: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Some studies have reported that the conventional intersegmental pedicle screws (4-screw fixation [4S]) device for thoracolumbar fractures was associated with inadequate reduction of fractured vertebrae, insufficient correction of kyphosis, and implant failure. Recently, a series of biomechanical studies has confirmed that the addition of intermediate fixation screws (6-screw fixation [6S]) could provide stronger fixation and better reduction of fractured vertebrae. Nevertheless, the clinical and radiologic efficacy of the additional intermediate screws remains unclear. METHODS: A meta-analysis of randomized controlled trials was used to compare clinical and radiologic outcomes and complications of posterior pedicle screws combined with intermediate screws fixation versus conventional intersegmental pedicle screw fixation. We comprehensively searched MEDLINE, OVID, and Springer according to a search strategy, selecting articles based on inclusion criteria, and extracted data from these reports. Risk of bias in included studies was assessed. Pooled estimates and corresponding 95% confidence intervals were calculated. RESULTS: Six randomized controlled trials involving 310 patients were evaluated in this meta-analysis. Pooled estimates showed statistically similar baseline characteristics, hospital stays, postoperative visual analog scale scores, and infection rates between the 4S group and the 6S group. The 6S group had significantly less correction loss of segmental angle and of anterior vertebral height compression, and lower implant failure rate. The 6S group also showed a slightly longer operative time and more blood loss than did the 4S group. CONCLUSIONS: Based on our analysis, the combined intermediate screws fixation technique was associated with significantly improved radiologic outcomes but did not seem to compromise other perioperative outcomes.

The Spinal Cord Line Can Predict Postoperative Recovery for Multilevel Cervical Spondylotic Myelopathy.

OBJECTIVE: To report a new index, the spinal cord (SC) line, and a new classification to predict postoperative recovery effect in patients with multilevel cervical spondylotic myelopathy (CSM). METHODS: On T2-weighted magnetic resonance imaging (MRI) of the cervical spine, point A is the posteroinferior point of the spinal cord at C2, and point B is the posterosuperior point of the spinal cord at C7. The SC line is defined as a line connecting A and B. The posterior surface of the compressor at the compression level does not exceed the line in SC line type I, touches the line in type II, and exceeds the line in type III. Between January 2010 and January 2015, 121 patients with multilevel CSM who underwent surgery through an anterior approach (anterior cervical corpectomy with fusion or anterior cervical discectomy and fusion) or a posterior approach (laminoplasty or laminectomy) in our hospital were studied retrospectively. The patients were classified into 3 groups according to SC line type (I, II, or III). RESULTS: In the anterior surgical approach group, the Japanese Orthopaedic Association (JOA) recovery rate at the last follow-up was 84.88 ± 3.06% for SC line type I, 78.05 ± 2.89% for type II, and 68.69 ± 3.21% for type III. In the posterior surgical approach group, the JOA recovery rate at last follow-up was 69.35 ± 8.73% for type I, 58.05 ± 5.88% for type II, and 47.98 ± 4.31% for type III. The anterior surgery approach was associated with a higher postoperative recovery rate than the posterior surgery approach in type II and type III groups (type II anterior vs. type II posterior: 78.05 ± 2.89% vs. 58.05 ± 5.88%, P = 0.003; type III anterior vs. type III posterior: 68.69 ± 3.21% vs. 47.98 ± 4.31%, P = 0.001). In contrast, the anterior and posterior surgery were associated with similar postoperative recovery rates in the type I group (84.88 ± 3.06% vs. 69.35 ± 8.73%; P = 0.820). CONCLUSIONS: The SC line and its classifications can predict postoperative recovery in patients with multilevel CSM.

Zero-Profile Spacer Versus Cage-Plate Construct in Anterior Cervical Diskectomy and Fusion for Multilevel Cervical Spondylotic Myelopathy: Systematic Review and Meta-Analysis.

BACKGROUND: Anterior cervical diskectomy and fusion with plate-screw construct has been gradually applied for multilevel cervical spondylotic myelopathy in recent years. However, long cervical plate was associated with complications including breakage or loosening of plate and screws, trachea-esophageal injury, neurovascular injury, and postoperative dysphagia. To reduce these complications, the zero-profile spacer has been introduced. This meta-analysis was performed to compare the clinical and radiologic outcomes of zero-profile spacer versus cage-plate construct for the treatment of multilevel cervical spondylotic myelopathy. METHODS: We systematically searched MEDLINE, Springer, and Web of Science databases for relevant studies that compared the clinical and radiologic outcomes of zero-profile spacer versus cage and plate for multilevel cervical spondylotic myelopathy. Risk of bias in included studies was assessed. Pooled estimates and corresponding 95% confidence intervals were calculated. RESULTS: On the basis of predefined inclusion criteria, 7 studies with a total of 409 patients were included in this analysis. The pooled data revealed that zero-profile spacer was associated with a decreased dysphagia rate at 2, 3, and 6 months postoperatively when compared with the cage-plate group. Both techniques had similar perioperative outcomes, functional outcome, radiologic outcome, and dysphagia rate immediately and at >1-year after operation. CONCLUSIONS: On the basis of available evidence, zero-profile spacer was more effective in reducing postoperative dysphagia rate for multilevel cervical spondylotic myelopathy. Both devices were safe in anterior cervical surgeries, and they had similar efficacy in improving the functional and radiologic outcomes. More randomized controlled trials are needed to compare these 2 devices.

Cervical digit in a child: A case report.

BACKGROUND: A "digit-like" bone is a rare developmental anomaly that is usually seen in the pelvic or thoracic regions. Such an anomaly in the cervical spine is extremely rare and few cases have been reported. We present a patient with an anomalous bone posterior to a cervical vertebra. The patient was admitted to our hospital with a gradually growing hard neck mass and esthetic complaints. Physical examination, radiographs, reconstructed computed tomography, and magnetic resonance imaging revealed a digit-like bone posterior to the cervical spine. The patient was diagnosed with a "cervical digit." Through a posterior midline approach, the anomalous bone was excised because of its gradually increasing size and esthetic complaints. RESULTS: Intraoperatively, the bony mass was found to have a pseudoarticulation with the spinous process of C5 (the fifth cervical vertebra). The specimen consisted of normal bone and cartilage. The child returned to a normal life postoperatively with no symptoms. There was no recurrence at the 2-year follow-up. CONCLUSION: A congenital cervical digit is a rare deformity. A detailed clinical workup and advanced imaging examinations are useful for diagnosing such conditions. Esthetic complaints contribute to surgical indications. This is the first cervical digit managed with surgical excision of the anomalous bone and had a favorable outcome.