Trabecular Formation Research Articles

The efficacy and safety of the internal medication therapy of the triple drugs for chronic subdural hematoma: Retrospective analysis

The recurrence of chronic subdural hematoma (CSDH) after surgical treatment is a severe problem with no effective prevention method. This retrospective study aimed to investigate factors associated with CSDH recurrence after burr hole surgery and hematoma changes on computed tomography before surgery to examine prevention methods for recurrence. A total of 166 hematomas were enrolled in this study, with 139 patients undergoing burr hole surgery for CSDH. Among these patients, 17 (12 %) had recurrence. Propensity score matching was performed based on postoperative drug therapy, including goreisan, carbazochrome sodium sulfonate hydrate, and tranexamic aid, resulting in 39 matched cases in 0–2 and 3 drug therapy groups. The recurrence rates were 18 % for the 0–2-drug therapy group and 3 % for the 3-drug therapy group. Univariate analysis revealed that the use of 0–2 drugs was associated with a higher risk of CSDH recurrence (odds ratio [OR], 8.31; 95 % confidence interval [CI], 0.97–71.17; p = 0.05) compared to the use of 3 drugs. Multivariate regression analysis further confirmed that 0–2 drug therapy after surgery was associated with an increased risk of CSDH recurrence (OR, 11.06; 95 % CI, 1.16–105.4; p = 0.037). Additionally, 36 hematomas were evaluated before surgery, with hematoma changes such as lower density and new trabecular formation detected in 14 CSDHs (39 %). Multivariate regression analysis showed that 3-drug therapy was associated with more cases of hematoma change than 0–2-drug therapy (OR, 13.9; 95 % CI, 1.09–177.65; p = 0.043). The 3-drug therapy was effective in reducing the recurrence of hematoma after burr hole surgery and promoted hematoma thrombosis.

From Marrow to Bone and Fat: Exploring the Multifaceted Roles of Leptin Receptor Positive Bone Marrow Mesenchymal Stromal Cells.

The bone marrow (BM) stromal cell microenvironment contains non-hematopoietic stromal cells called mesenchymal stromal cells (MSCs). MSCs are plastic adherent, form CFU-Fs, and give rise to osteogenic, adipogenic, chondrogenic progenitors, and most importantly provide HSC niche factor chemokine C-X-C motif ligand 12 (CXCL12) and stem cell factor (SCF). Different authors have defined different markers for mouse MSC identification like PDGFR+Sca-1+ subsets, Nestin+, or LepR+ cells. Of these, the LepR+ cells are the major source of SCF and CXCL12 in the BM microenvironment and play a major role in HSC maintenance and hematopoiesis. LepR+ cells give rise to most of the bones and BM adipocytes, further regulating the microenvironment. In adult BM, LepR+ cells are quiescent but after fracture or irradiation, they proliferate and differentiate into mesenchymal lineage osteogenic, adipogenic and/or chondrogenic cells. They also play a crucial role in the steady-state hematopoiesis process, as well as hematopoietic regeneration and the homing of hematopoietic stem cells (HSCs) after myeloablative injury and/or HSC transplantation. They line the sinusoidal cavities, maintain the trabeculae formation, and provide the space for HSC homing and retention. However, the LepR+ cell subset is heterogeneous; some subsets have higher adipogenic potential, while others express osteollineage-biased genes. Different transcription factors like Early B cell factor 3 (EBF3) or RunX2 help maintain this balance between the self-renewing and committed states, whether osteogenic or adipogenic. The study of LepR+ MSCs holds immense promise for advancing our understanding of HSC biology, tissue regeneration, metabolic disorders, and immune responses. In this review, we will discuss the origin of the BM resident LepR+ cells, different subtypes, and the role of LepR+ cells in maintaining hematopoiesis, osteogenesis, and BM adipogenesis following their multifaceted impact.

Role of Ultrasound and Ultrasound-Based Prediction Model in Differentiating Follicular Thyroid Carcinoma From Follicular Thyroid Adenoma.

This study aims to identify distinct ultrasound (US) characteristics for distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and construct a user-friendly preoperative risk stratification model for thyroid follicular neoplasms. In this retrospective study, patients diagnosed with pathologically confirmed FTA or FTC and undergoing US examinations between July 2017 and June 2021 were designated as the training cohort, and those from July 2021 to June 2023 were enrolled as the external validation set. We systematically assessed and compared the sonographic and clinical characteristics of FTC and FTA. Univariable and multivariable logistic regression analyses were used to assess the association of US features with FTC in the training set. A prediction nomogram model, incorporating US features independently associated with FTC, was developed and validated externally to assess its performance. A total of 645 patients (FTA/FTC = 530/115) were included in the training set, while 197 patients (FTA/FTC = 165/32) constituted the validation set. In the training set, solid composition, hypo-echogenicity, irregular margin, calcification, protrusion sign, trabecular formation, absent or thick halo, and mainly central hypervascularity were identified as independent factors associated with FTC. The prediction nomogram model constructed using these variables showed good performance in differentiating FTC from FTA with an area under the curve of 0.948 in the training set and 0.915 in the validation set. The preoperative nomogram model constructed based on US features serves as an effective tool for the risk stratification of thyroid follicular neoplasms.

Periostin Promotes the Proliferation, Differentiation and Mineralization of Osteoblasts from Ovariectomized Rats.

Perimenopausal period causes a significant amount of bone loss, which results in primary osteoporosis (OP). The Periostin (Postn) may play important roles in the pathogenesis of OP after ovariectomized (OVX) rats. To identify the roles of Postn in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB) in OVX rats, we investigated the expression of Wnt/β-catenin signaling pathways in BMSC-OB and the effects of Postn on bone formation by development of BMSC-OB cultures. Twenty-four female Sprague-Dawley rats at 6 months were randomized into 3 groups: sham-operated (SHAM) group, OVX group and OVX+Postn group. The rats were killed after 3 months, and their bilateral femora and tibiae were collected for BMSC-OB culture, Micro-CT Analysis, Bone Histomorphometric Measurement, Transmission Electron Microscopy and Immunohistochemistry Staining. The dose/time-dependent effects of Postn on the proliferation, differentiation and mineralization of BMSC-OB and the expression of osteoblastic markers were measured in in vitro experiments. We found increased Postn increased bone mass, promoted bone formation of trabeculae, Wnt signaling and the osteogenic activity in osteoblasts in sublesional femur. Postn have the function to enhance cell proliferation, differentiation and mineralization at a proper concentration and incubation time. Interestingly, in BMSC-OB from OVX rats treated with the different dose of Postn, the osteoblastic markers expression and Wnt/β-catenin signaling pathways were significantly promoted. The direct effect of Postn may lead to inhibit excessive bone resorption and increase bone formation through the Wnt/β-catenin signaling pathways after OVX. Postn may play a very important role in the pathogenesis of OP after OVX.

Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos.

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation.

Hierarchically Assembled Nanofiber Scaffold Guides Long Bone Regeneration by Promoting Osteogenic/Chondrogenic Differentiation of Endogenous Mesenchymal Stem Cells.

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2(BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.

Si-Zhi Wan regulates osteoclast autophagy in osteoporosis through the AMPK signaling pathway to attenuate osteoclastogenesis.

The mechanisms underlying the therapeutic effects of Si-Zhi Wan (SZW), a traditional Chinese medicine used to treat osteoporosis (OP), remain unknown. This study investigated the therapeutic effects of SZW on mice that underwent ovariectomy (OVX) and underlying mechanisms thereof. We established an in vivo model of OP by performing OVX in mice. Microcomputed tomography (Micro-CT) was used to assess changes in bone characteristics of mice following SZW administration for 4 weeks. H&E staining revealed alterations in bone tissues of mice. Osteoclastogenesis in mouse bone tissue was observed using tartrate-resistant acid phosphatase staining and western blotting. Furthermore, we examined the impact of SZW on osteoclastogenesis in vitro using receptor activator of nuclear factor kappa-B ligand (RANKL). Finally, we explored the regulatory effects of SZW on osteoclast autophagy and the AMPK pathway. The results demonstrated that high-dose SZW reversed changes in bone density parameters caused by OVX, including bone volume (BV), BV/total volume, trabecular number, and trabecular spacing (P = 0.0007, 0.0035, 0.0114, and 0.0182, respectively), and stimulated the formation of bone trabeculae in mice (P < 0.0001). Furthermore, SZW suppressed osteoclast formation in mice with OVX and inhibited osteoclast formation induced by RANKL. Mechanistically, SZW inhibited osteoclast precursor cell autophagy through the AMPK pathway. SZW effectively inhibited the autophagy of osteoclast precursors by regulating the AMPK pathway, thereby exerting anti-osteoclastogenic effects and serving as an alternative therapy for OP.

The Role of Aryl Hydrocarbon Receptor in Bone Biology.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of AhR in bone biology and identifying novel signaling pathways in musculoskeletal pathologies using the GEO dataset. The GEO2R analysis identified 8 genes (CYP1C1, SULT6B1, CYB5A, EDN1, CXCR4B, CTGFA, TIPARP, and CXXC5A) involved in the AhR pathway, which play a pivotal role in bone remodeling. The AhR knockout in hematopoietic stem cells showed alteration in several novel bone-related transcriptomes (eg, Defb14, ZNF 51, and Chrm5). Gene Ontology Enrichment Analysis demonstrated 54 different biological processes associated with bone homeostasis. Mainly, these processes include bone morphogenesis, bone development, bone trabeculae formation, bone resorption, bone maturation, bone mineralization, and bone marrow development. Employing Functional Annotation and Clustering through DAVID, we further uncovered the involvement of the xenobiotic metabolic process, p450 pathway, oxidation-reduction, and nitric oxide biosynthesis process in the AhR signaling pathway. The conflicting evidence of current research of AhR signaling on bone (positive and negative effects) homeostasis may be due to variations in ligand binding affinity, binding sites, half-life, chemical structure, and other unknown factors. In summary, our study provides a comprehensive understanding of the underlying mechanisms of the AhR pathway in bone biology.

Total Flavonoids from Rhizoma Drynariae (Gusuibu) Alleviates Diabetic Osteoporosis by Activating BMP2/Smad Signaling Pathway.

Diabetic osteoporosis (DOP) is a widespread public health problem. The flavonoids of Rhizoma Drynariae (RDF) have a clear preventive and therapeutic effect on osteoporosis (OP), but it is not yet clear whether RDF has an anti-DOP and whether its mechanism is related to the activation of the BMP2/Smad signaling pathway. The current study aimed to study this effect of RDF in DOP rats and the possible involvement of the BMP2/Smad signaling pathway activation. Following intragastric administration of RDF for 12 weeks, the body weight, blood glucose, and the bone histopathological changes detected by hematoxylin-eosin (H&E) and calcein staining were monitored, while bone parameters were regularly assessed from observations made by micro-CT. At the end of the experiment, the expression of Bmp2, Bmpr1a, Runx2, and Smad4/5 genes was detected by real-time PCR (RT-PCR). Meanwhile, western blotting or immunohistochemical staining monitored the protein expressions of BMP2, RUNX2, and SMAD5 in the bone. The results firstly indicated that RDF significantly alleviated the signs and symptoms of DOP, which manifested as improved body weight and blood glucose. As obtained from the results of histopathology and micro-CT, RDF could promote the formation of bone trabeculae and alter several the bone microstructure parameters, including an increase in the bone volume/total volume (BV/TV), connective density (Conn-Dens), and trabecular bone number (Tb.N), as well as a decrease in the trabecular spacing (Tb.Sp). The western blotting analysis and RT-PCR results also confirmed that RDF could markedly increase the mRNA expression levels of Bmp2, Bmpr1α, Smad4, Runx2, and Smad5 in the bone, as well as the corresponding protein expression levels of BMP2, RUNX2, and SMAD5. These results reveal that RDF can activate the BMP2/Smad signaling pathway, thus promoting bone remodeling in DOP rats. RDF can increase bone trabeculae and bone mineral density by promoting bone formation and inhibiting bone absorption, thereby playing a role in improving DOP. This effect is related to the regulation of the BMP2/Smad signaling pathway.

Nrg1 Regulates Cardiomyocyte Migration and Cell Cycle in Ventricular Development.

Cardiac ventricles provide the contractile force of the beating heart throughout life. How the primitive endocardium-layered myocardial projections called trabeculae form and mature into the adult ventricles is of great interest for biology and regenerative medicine. Trabeculation is dependent on the signaling protein Nrg1 (neuregulin-1). However, the mechanism of action of Nrg1 and its role in ventricular wall maturation are poorly understood. We investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development using confocal imaging, transcriptomics, and biochemical approaches in mice with cardiac-specific inactivation or overexpression of Nrg1. Analysis of cardiac-specific Nrg1 mutant mice showed that the transcriptional program underlying cardiomyocyte-oriented cell division and trabeculae formation depends on endocardial Nrg1 to myocardial ErbB2 (erb-b2 receptor tyrosine kinase 2) signaling and phospho-Erk (phosphorylated extracellular signal-regulated kinase; pErk) activation. Early endothelial loss of Nrg1 and reduced pErk activation diminished cardiomyocyte Pard3 and Crumbs2 (Crumbs Cell Polarity Complex Component 2) protein and altered cytoskeletal gene expression and organization. These alterations are associated with abnormal gene expression related to mitotic spindle organization and a shift in cardiomyocyte division orientation. Nrg1 is crucial for trabecular growth and ventricular wall thickening by regulating an epithelial-to-mesenchymal transition-like process in cardiomyocytes involving migration, adhesion, cytoskeletal actin turnover, and timely progression through the cell cycle G2/M phase. Ectopic cardiac Nrg1 overexpression and high pErk signaling caused S-phase arrest, sustained high epithelial-to-mesenchymal transition-like gene expression, and prolonged trabeculation, blocking compact myocardium maturation. Myocardial trabecular patterning alterations resulting from above- or below-normal Nrg1-dependent pErk activation were concomitant with sarcomere actin cytoskeleton disorganization. The Nrg1 loss- and gain-of-function transcriptomes were enriched for Yap1 (yes-associated protein-1) gene signatures, identifying Yap1 as a potential downstream effector. Furthermore, biochemical and imaging data reveal that Nrg1 influences pErk activation and Yap1 nuclear-cytoplasmic distribution during trabeculation. These data establish the Nrg1-ErbB2/ErbB4-Erk axis as a crucial regulator of cardiomyocyte cell cycle progression and migration during ventricular development.

Bone strength is reduced in a neonatal androgenized rat model

BackgroundWhether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and reproductive features of women with PCOS, and we aimed to use it to investigate the impact of androgens on microarchitecture (by micro-CT), bone mechanical strength, bone formation and resorption markers in rats with intact ovaries (SHAM) who underwent oophorectomy. MethodsWistar rats (Rattus norvegicus albinus) were employed for the experiments in this study. The protocol of androgenization consisted of the application of 1.25 mg s.c. testosterone propionate beteween days 2–5 of life, while the controls received the same amount of corn oil s.c. as previously established. Androgenized SHAM rats exhibited chronic anovulation identified by vaginal cytology and a reduction in the proportion of corpus luteum in the ovary in comparison to control SHAM rats. The realization of the ovariectomy or SHAM procedure occurred on Day 100 of life. All groups (n = 8) were followed-up for 180 days to address the study endpoints. ResultsMicro-CT from androgenized female rats (SHAM) showed a divergence between the trabecular and cortical bone profiles. Compared to SHAM controls, these rats had an increase in trabecular bone mass with a diminution in bone resorption C-terminal telopeptide of type 1 collagen (CTX) (p < 0.05), a concomitant decrease in cortical area and thickness in the femur, and a reduction in the strength of the femur on the mechanical test (p < 0.01). ConclusionsOur results suggest that a reduction in the cortical thickness and cortical area observed in PCOS model rats was associated with a reduced strength of the femur, despite increased trabecular formation. Ovariectomy in the androgenized OVX group limited the progression rate of cortical bone loss, resulting in bone resistance and cortical thickness comparable to those observed in the control OVX group.

Condensing Osteitis – A Review and Case Report

Condensing osteitis is pathological lesions of the maxillomandibular region which is seen in root apex of long standing untreated carious lesions or tooth having inappropriate endodontic treatment and generally occurs as a result of body’s defence mechanism against the infection. Dense trabeculae formation is seen within the bone marrow which appears as a radiopaque lesion near the apex of the affected tooth. Diagnosis of condensing osteitis depends on proper clinical and radiographic evaluation. In the present case report, condensing osteitis in a 12-year female is reported and with adequate endodontic procedure, healing and regression were seen after 6 months of follow-up.

Coexisting Infantile Hepatic Hemangioma and Hepatoblastoma in a Neonate: A Case Report.

Infantile hepatic hemangioma and hepatoblastoma are the most common benign and malignant tumors of the liver in the neonatal and early childhood periods, respectively. However, the simultaneous occurrence of these 2 tumors in the same liver lesion is very rare. We report a case of a newborn infant diagnosed with a liver mass by ultrasound examination 4 days after birth. Serum alpha-fetoprotein (AFP) was elevated for his age (32,881.7 ng/mL). The liver mass was resected. Macroscopically, an externally protruding mass measuring 6 × 4 × 3.5 cm was identified. Microscopically, we observed the coexistence of infantile hepatic hemangioma and epithelial hepatoblastoma components within the tumor. The infantile hepatic hemangioma component was composed of multiple small vascular channels lined by endothelial cells. In the hepatoblastoma component, tumor cells were arranged in a 2- to 3-cell-thick trabecular formation. Immunohistochemistry indicated that the tumor cells in the infantile hepatic hemangioma component expressed CD34, CD31, FLI1, and ERG, and those in the hepatoblastoma component expressed hepatocyte, keratin AE1/AE3 and keratin 8, glypican 3, glutamine synthetase, and AFP. Pathological examination confirmed the presence of an infantile hepatic hemangioma combined with epithelial hepatoblastoma (fetal type). The boy did not undergo chemotherapy after the operation. Regular follow-up through serum AFP levels and liver ultrasound for 16 months to date show that the serum AFP levels decreased continuously to normal levels, with no signs of tumor recurrence or metastasis. The coexistence of infantile hepatic hemangioma and hepatoblastoma is rare. Hepatoblastoma should be considered in neonates with liver tumors and elevated AFP.

Osteoregeneration of Critical-Size Defects Using Hydroxyapatite-Chitosan and Silver-Chitosan Nanocomposites.

Bone is a natural nanocomposite composed of proteins and minerals that can regenerate itself. However, there are conditions in which this process is impaired, such as extensive bone defects and infections of the bone or surrounding tissue. This study evaluates the osteoregenerative capacity of bone grafting materials in animals with induced bone defects. Colloidal chitosan dispersion nanocomposites, nanohydroxyapatite−chitosan (NHAP-Q) and nanosilver−chitosan (AgNP-Q), were synthesized and characterized. Non-critical-size defects in Wistar rats were used to evaluate the material’s biocompatibility, and critical-size defects in the calvarias of guinea pigs were used to evaluate the regenerative capacity of the bones. Moreover, the toxicity of the nanocomposites was evaluated in the heart, liver, spleen, kidneys, and skin. Histological, radiographic, and electron microscopy tests were also performed. The results showed that neither material produced pathological changes. Radiographic examination showed a significant reduction in defects (75.1% for NHAP-Q and 79.3% for AgNP-Q), angiogenesis, and trabecular formation. A toxicological assessment of all the organs did not show changes in the ultrastructure of tissues, and the distribution of silver was different for different organs (spleen > skin > heart > kidney > liver). The results suggest that both materials are highly biocompatible, and AgNP-Q achieved similar bone regeneration to that reported with autologous bone. The main research outcome of the present study was the combination of two types of NPs to enhance antimicrobial and osteoregeneration activities. These colloidal chitosan dispersions show promise as future biomaterials in the medical field for applications in fast-healing fractures, including broken bones in the oral cavity and hip replacement infections.

SDF-1 induces directional chemotaxis of BMSCs at the intervertebral fusion site and promotes osteogenic differentiation by regulating Wnt/β-catenin in the bone marrow chimera spinal intervertebral fusion mouse model.

Clinical observations show that the current spinal fusion with internal fixation has a nonfusion rate of 5%-35%; however, methods to promote spinal fusion are limited. This study aimed to investigate the role of SDF-1-induced directional chemotaxis of BMSCs in bone marrow chimera spinal intervertebral fusion mouse model. BMSCs were isolated from bone marrow and identified by detecting CD44/CD34 positive cells. BMSCs (GFP-BMSCs) were labeled with GFP for tracking in vivo. Mice were inoculated with GFP-BMSCs to construct bone marrow chimera spinal intervertebral fusion model, which were divided into BM-SIF model, BM-SIF+SDF-1, BM-SIF+SDF-1-Anta group. The callus area of intervertebral fusion site was detected by radiology. HE staining was used to detect trabeculae formation. Expressions of osteogenic molecules and fibroblast markers were detected by RT-PCR and Western blotting. GFP-BMSCs showed obvious osteogenic and adipogenic differentiation ability, according to oil-red O and alizarin-red staining. Bone marrow chimera spinal intervertebral fusion mouse model was successfully established, with efficient localization of GFP-BMSCs at intervertebral fusion site. SDF-1 significantly promoted bone trabeculae formation in callus at intervertebral fusion site. SDF-1 significantly increased osteogenic molecules transcription/expression in callus at intervertebral bone graft fusion site of mice; however, SDF-1-Anta (AMD3100) significantly decreased osteogenic molecules transcrition/expression, compared to those of mice from the BM-SIF model group (p < 0.05). SDF-1 markedly induced and SDF-1-Anta significantly decreased fibroblast proliferations in the callus at the intervertebral fusion site of mice, compared to those of mice from the BM-SIF model group (p < 0.05). SDF-1 enhanced expression of Wnt10b and β-catenin in callus at intervertebral fusion site of mice compared to mice of the BM-SIF model group (p < 0.05). In conclusion, SDF-1 induced directional chemotaxis of BMSCs to the intervertebral fusion site and promoted osteogenic differentiation in bone marrow chimera spinal intervertebral fusion mice by regulating Wnt/β-catenin pathway and modulating the proliferation of BMSCs.

Histological evaluation of wound healing by topical phenytoin application on extraction socket: anin vivostudy in albino Wistar rats

Objective:To investigate the effects of topical phenytoin application on wound healing of extraction socket of albino Wistar rats.Materials and methods:Thirty-six albino Wistar rats were randomly divided into Group A (control), B (1% phenytoin mucoadhesive paste), and C (mucoadhesive paste without phenytoin). All animals were anesthetized followed by first molar extraction. Group A did not receive any agent, whereas, Group B and C received daily application of their respective pastes. Four animals from each group were sacrificed on day 7, 14, and 21 and analyzed histologically.Results:No significant difference was found in blood vessel count among the groups. Statistical increase in percentage of fibroblast in Group B was found as compared with other groups at day 7, whereas, no significant difference was found among groups at day 14. Day 21 showed significant decrease in percentage of fibroblasts in Group B (p-value &lt; 0.001) as compared with Group A and C. Increase in percentage of bone trabeculae in Group B was observed on day 7, 14, and 21 with a significant difference (p-value &lt; 0.05) as compared to Group A and C.Conclusion:Topical application of phenytoin promoted fibroblast proliferation and bone trabeculae formation during healing of extraction socket in rats.

Development of ventricular trabeculae affects electrical conduction in the early endothermic heart.

The ventricular trabeculae play a role, among others, in the impulse spreading in ectothermic hearts. Despite the morphological similarity with the early developing hearts of endotherms, this trabecular function in mammalian and avian embryos was poorly addressed. We simulated impulse propagation inside the looping ventricle and revealed delayed apical activation in the heart with inhibited trabecular growth. This finding was corroborated by direct imaging of the endocardial surface showing early activation within the trabeculae implying preferential spreading of depolarization along with them. Targeting two crucial pathways of trabecular formation (Neuregulin/ErbB and Nkx2.5), we showed that trabecular development is also essential for proper conduction patterning. Persistence of the slow isotropic conduction likely contributed to the pumping failure in the trabeculae-deficient hearts. Our results showed the essential role of trabeculae in intraventricular impulse spreading and conduction patterning in the early endothermic heart. Lack of trabeculae leads to the failure of conduction parameters differentiation resulting in primitive ventricular activation with consequent impact on the cardiac pumping function.

The Ability of Biodegradable Thermosensitive Hydrogel Composite Calcium-Silicon-Based Bioactive Bone Cement in Promoting Osteogenesis and Repairing Rabbit Distal Femoral Defects.

Osteoporotic vertebral compression fractures are a global issue affecting the elderly population. To explore a new calcium silicate bone cement, polylactic acid (PLGA)–polyethylene glycol (PEG)–PLGA hydrogel was compounded with tricalcium silicate (C3S)/dicalcium silicate (C2S)/plaster of Paris (POP) to observe the hydration products and test physical and chemical properties. The cell compatibility and osteogenic capability were tested in vitro. The rabbit femoral condylar bone defect model was used to test its safety and effectiveness in vivo. The addition of hydrogel did not result in the formation of a new hydration product and significantly improved the injectability, anti-washout properties, and in vitro degradability of the bone cement. The cholecystokinin octapeptide-8 method showed significant proliferation of osteoblasts in bone cement. The Alizarin red staining and alkaline phosphatase activity test showed that the bone cement had a superior osteogenic property in vitro. The computed tomography scan and gross anatomy at 12 weeks after surgery in the rabbit revealed that PLGA-PEG-PLGA/C3S/C2S/POP was mostly degraded, with the formation of new bone trabeculae and calli at the external orifice of the defect. Thus, PLGA-PEG-PLGA/C3S/C2S/POP composite bone cement has a positive effect on bone repair and provides a new strategy for the clinical application of bone tissue engineering materials.

Transcriptional sequencing analysis reveals the potential use of deer antler for “tonifying the kidney and strengthening bone”

BackgroundIt is recorded in the Chinese Pharmacopoeia that deer antlers can be used to tonify the kidney and strengthen bone. Although numerous studies have demonstrated that deer antler has protective effects on the kidney and bone, its molecular mechanisms remain to be elucidated. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney.MethodsWater extract of pilose antler was prepared and then filtered through a 0.45 μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. Rats were treated with deer antler extract (DAE) prepared in advance, and gene regulatory network in the kidney and bone was detected by RNA-Seq technique. Micro-CT was used to detect bone trabecular formation, bone mineral density (BMD) and bone volume fraction (BV/TV).ResultsThe results demonstrate that DAE could jointly heighten renal function by maintaining renal homeostasis, combating renal fibrosis, and reducing renal inflammation by regulating ion transport. Furthermore, DAE can strengthen the bone system by stimulating osteoblast differentiation and regulating bone regeneration and the bone marrow microenvironment. Micro-CT results confirmed that DAE can promote bone trabecular formation and increase BMD and BV/TV. We also identified many genes that can regulate both the kidney and bone simultaneously, which explained the theory of “kidney governing bone” at the molecular level and provided possible strategies for further application of this theory to treat diseases.ConclusionsDAE enhances renal function, maintains renal homeostasis, positively regulates skeletal system development, and increases bone mineral density. The underlying mechanism involves improving the expression levels of functional genes involved in renal function and regulation and repair, as well as genes that positively regulate skeletal system development.

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review.

Background and ObjectiveLeft ventricular noncompaction (LVNC) is a cardiomyopathy characterized by excessive trabecular formation and deep recesses in the ventricular wall, with a bilaminar structure consisting of an endocardial noncompaction layer and an epicardial compacted layer. Although genetic variants have been reported in patients with LVNC, understanding of LVNC and its pathogenesis has not yet been fully elucidated. We addressed the latest findings on genes reported to be associated with LVNC morphogenesis and possible pathologies to understand the diverse spectrum between genotype and phenotype in LVNC. Also, the latest findings and issues related to the diagnosis of LVNC were summarized.MethodsThis article is written as a commentary narrative review and will provide an update on the current literature and available data on common forms of LVNC published in the past 30 years in English through to May 2022 using PubMed.Key Content and FindingsFamilial forms of LVNC are frequent, and autosomal dominant mode of inheritance has been predominantly observed. Several of the candidate causative genes are also mutated in other cardiomyopathies, suggesting a possible shared molecular and/or cellular etiology. The most common gene functions were sarcomere function whereas genes in mice LVNC models were involved in heart development. Echocardiography and cardiac magnetic resonance imaging (CMR) are useful for diagnosis although there are no unified criteria due to overdiagnosis of imaging, poor consistency between techniques, and lack of association between trabecular severity and adverse clinical outcomes.ConclusionsThis review reflects the current lack of clarity regarding the pathogenesis and significance of LVNC and showed the complexity of imaging diagnostic criteria, interpretation of the role of LVNC as a cause, and uncertainty regarding the specific genetic basis of LVNC.