CD44, an adhesion molecule that binds to the extracellular matrix, primarily to hyaluronan (HA), has been implicated in cancer cell migration, invasion, and metastasis. CD44 has also recently been ...recognized as a marker for stem cells of several types of cancer. However, the roles of CD44 in the development of bone metastasis are unclear. Here, we addressed this issue by using bone metastatic cancer cell lines, in which CD44 was stably knocked down. Tumor sphere formation and cell migration and invasion were significantly inhibited by CD44 knockdown. Furthermore, the downregulation of CD44 markedly suppressed tumorigenicity and bone metastases in nude mice. Of note, the number of osteoclasts decreased in the bone metastases. Microarray analysis revealed that the expression of HA synthase 2 was downregulated in CD44-knockdown cells. The localization of HA in the bone metastatic tumors was also markedly reduced. We then examined the roles of CD44-HA interaction in bone metastasis using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis. 4-MU decreased tumor sphere and osteoclast-like cell formation in vitro. Moreover, 4-MU inhibited bone metastases in vivo with reduced number of osteoclasts. These results collectively suggest that CD44 expression in cancer cells promotes bone metastases by enhancing tumorigenicity, cell migration and invasion, and HA production. Our results also suggest the possible involvement of CD44-expressing cancer stem cells in the development of bone metastases through interaction with HA. CD44-HA interaction could be a potential target for therapeutic intervention for bone metastases.
Mucopolysaccharidoses (MPS) are a group of inherited, multisystem, lysosomal storage disorders involving specific lysosomal enzyme deficiencies that result in the accumulation of glycosaminoglycans ...(GAG) secondary to insufficient degradation within cell lysosomes. GAG accumulation affects both primary bone formation and secondary bone growth, resulting in growth impairment. Typical spinal manifestations in MPS are atlantoaxial instability, thoracolumbar kyphosis/scoliosis, and cervical/lumbar spinal canal stenosis. Spinal disorders and their severity depend on the MPS type and may be related to disease activity. Enzyme replacement therapy or hematopoietic stem cell transplantation has advantages regarding soft tissues; however, these therapeutic modalities are not effective for bone or cartilage and MPS-related bone deformity including the spine. Because spinal disorders show the most serious deterioration among patients with MPS, spinal surgeries are required although they are challenging and associated with high anesthesia-related risks. The aim of this review article is to provide the current comprehensive knowledge of representative spinal disease in MPS and its surgical management, including the related pathology, symptoms, and examinations.
This letter discusses the characteristics of orbital angular momentum (OAM) of hybrid mode in the cylindrical corrugated waveguide. The well-known discussion of the OAM in Laguerre-Gaussian (L-G) ...laser fields is applied to the hybrid mode of the corrugated waveguide. The analytical discussions of the OAM are also investigated by numerical simulations of the finite-difference time-domain (FDTD) method. It is found that the hybrid modes in the corrugated waveguide carry well-defined OAM.
In this paper we determine the automorphism groups of the profinite braid groups with four or more strings in terms of the profinite Grothendieck-Teichm\"uller group.
During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it ...has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1+-PDL cells after tooth extraction was analyzed using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. After the final administration of tamoxifen to iGli1/Tomato mice, Gli1/Tomato+ cells were rarely detected in the PDL. One day after the tooth extraction, although inflammatory cells appeared in the tooth socket, Periostin+ PDL-like tissues having a few Gli1/Tomato+ cells remained near the alveolar bone. Three days after the extraction, the number of Gli1/Tomato+ cells increased as evidenced by numerous PCNA+ cells in the socket. Some of these Gli1/Tomato+ cells expressed BMP4 and Phosphorylated (P)-Smad1/5/8. After seven days, the Osteopontin+ bone matrix was formed in the tooth socket apart from the alveolar bone. Many Gli1/Tomato+ osteoblasts that were positive for Runx2+ were arranged on the surface of the newly formed bone matrix. In the absence of Gli1+-PDL cells in Gli1-CreERT2/Rosa26-loxP-stop-loxP-tdDTA (iGli1/DTA) mice, the amount of newly formed bone matrix was significantly reduced in the tooth socket. Therefore, these results collectively suggest that Gli1+-PDL cells differentiate into osteoblasts to form the bone matrix in the tooth socket; thus, this differentiation might be regulated, at least in part, by bone morphogenetic protein (BMP) signaling.
•Gli1+-periodontal ligament (PDL) cells remained in the tooth socket.•After tooth extraction, Gli1+ cells in the PDL differentiated into osteoblasts.•BMP signaling might relate the osteoblast differentiation of Gli1+-PDL cells.
Orthodontic tooth movement (OTM) induces bone formation on the alveolar bone of the tension side; however, the mechanism of osteoblast differentiation is not fully understood. Gli1 is an essential ...transcription factor for hedgehog signaling and functions in undifferentiated cells during embryogenesis. In this study, we examined the differentiation of Gli1+ cells in the periodontal ligament (PDL) during OTM using a lineage-tracing analysis. After the final administration of tamoxifen for 2 days to 8-week-old Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice, Gli1/Tomato+ cells were rarely observed near endomucin+ blood vessels in the PDL. Osteoblasts lining the alveolar bone did not exhibit Gli1/Tomato fluorescence. To move the first molar of iGli1/Tomato mice medially, nickel–titanium closed-coil springs were attached between the upper anterior alveolar bone and the first molar. Two days after OTM initiation, the number of Gli1/Tomato+ cells increased along with numerous PCNA+ cells in the PDL of the tension side. As some Gli1/Tomato+ cells exhibited positive expression of osterix, an osteoblast differentiation marker, Gli1+ cells probably differentiated into osteoblast progenitor cells. On day 10, the newly formed bone labeled by calcein administration during OTM was detected on the surface of the original alveolar bone of the tension side. Gli1/Tomato+ cells expressing osterix localized to the surface of the newly formed bone. In contrast, in the PDL of the compression side, Gli1/Tomato+ cells proliferated before day 10 and expressed type I collagen, suggesting that the Gli1+ cells also differentiated into fibroblasts. Collectively, these results demonstrate that Gli1+ cells in the PDL can differentiate into osteoblasts at the tension side and may function in bone remodeling as well as fibril formation in the PDL during OTM.
•Periodontal ligament harbors Gli1-expressing mesenchymal stem cells.•Mechanical stress induces Gli1+ cell differentiation into osteoblasts.•Gli1+ cell progenies might act as fibrous formation in the compression side.
The negative impact of cigarette smoking on bone union has been well documented. However, the impact of heated tobacco product (HTP) use on bone fracture-healing remains unclear. The present study ...investigated the effect of HTPs on preosteoblast viability, osteoblastic differentiation, and fracture-healing and compared the effects with those of conventional combustible cigarettes.
Cigarette smoke extracts (CSEs) were generated from combustible cigarettes (cCSE) and HTPs (hCSE). CSE concentrations were standardized by assessing optical density. Preosteoblast (MC3T3-E1) cells were incubated with normal medium, cCSE, or hCSE. The cell viability was assessed via MTT assay. After osteoblastic differentiation of CSE-exposed cells, alkaline phosphatase (ALP) activity was assessed. To assess the in vivo effects of CSEs, a femoral midshaft osteotomy was performed in a rat model; thereafter, saline solution, cCSE, or hCSE was injected intraperitoneally, and bone union was assessed on the basis of micro-computed tomography (μCT) and biomechanical analysis 4 weeks later.
MC3T3-E1 cell viability was reduced in a time and concentration-dependent manner when treated with either cCSE or hCSE. ALP activity after osteoblastic differentiation of cCSE-treated cells was significantly lower than that of both untreated and hCSE-treated cells (mean and standard deviation, 452.4 ± 48.8 untreated, 326.2 ± 26.2 cCSE-treated, and 389.9 ± 26.6 hCSE-treated mol/L/min; p = 0.002). Moreover, the levels of osteoblastic differentiation in untreated and hCSE-treated cells differed significantly (p < 0.05). In vivo assessment of the femoral midshaft cortical region revealed that both cCSE and hCSE administration significantly decreased bone mineral content 4 weeks after surgery compared with levels observed in untreated animals (107.0 ± 11.9 untreated, 94.5 ± 13.0 cCSE-treated, and 89.0 ± 10.1 mg/cm3 hCSE-treated; p = 0.049). Additionally, cCSE and hCSE-exposed femora had significantly lower bone volumes than unexposed femora. Biomechanical analyses showed that both cCSE and hCSE administration significantly decreased femoral maximum load and elastic modulus (p = 0.015 and 0.019).
HTP use impairs cell viability, osteoblastic differentiation, and bone fracture-healing at levels comparable with those associated with combustible cigarette use.
HTP use negatively affects bone fracture-healing to a degree similar to that of combustible cigarettes. Orthopaedic surgeons should recommend HTP smoking cessation to improve bone union.
Lumbar spinal stenosis (LSS) is a common disease in the elderly, mostly due to degenerative changes in the lumbar spinal complex. Decompression surgery is the standard surgical treatment for LSS. ...Classically, total laminectomy-which involves resection of the spinous process, entire laminae and medial facet-has been the standard decompression technique; however, it can cause post-surgical instability. To overcome this disadvantage, various minimally invasive techniques that preserve the stabilization structures of the spine have been developed, and surgeons have begun to re-evaluate decompression surgery from the standpoint of reduced invasiveness and cost. More than two decades have passed since the introduction of microendoscopic spine surgery, and studies continue to shed light on its advantages and limitations as new knowledge becomes available. This article is a narrative review of the available literature, along with authors' experience, regarding the indications, surgical techniques, clinical outcomes, and limitations/complications of microendoscopic decompression for LSS.
In this study, fuzz structures in tungsten surfaces are artificially generated using the midpoint displacement algorithm (MDA) based on the random fractal. The finite-difference time-domain (FDTD) ...method is employed to simulate electromagnetic wave propagation in the fuzz structures with different fractal dimension sizes. To analyze electromagnetic penetrations and reflections around the fuzz structures, we adopt the three-dimensional empirical mode decomposition (TEMD) to decompose simulation results by FDTD in the spatial frequency domain. The computation results showed that the distribution of electric field intensity is decomposed into 3-D intrinsic mode functions (IMFs), indicating resonances triggered by electromagnetic waves hitting the fuzz structures in the tungsten surface from high spatial frequency to low spatial frequency. These decomposed IMFs revealed the optical properties of fuzz structures regarding the relationship between fractal dimension sizes and the electromagnetic penetrations and reflections in the tungsten surface.
Background:
The optimal graft choice between the bone–patellar tendon–bone (BPTB) and the quadriceps tendon remains controversial. Studies evaluating the microscopic anatomy of the quadriceps ...tendon–patellar bone (QTB) and BPTB grafts for anterior cruciate ligament (ACL) reconstruction are currently lacking.
Hypothesis:
The relationship between post–ACL reconstruction graft bending angle (GBA) and the angle corresponding to the GBA (cGBA) would indicate that the BPTB can bend more than the QTB at the femoral tunnel aperture.
Study Design:
Controlled laboratory study.
Methods:
Twenty paired human cadaveric knees fixed at <10° of knee joint flexion (mean age, 82.5 years) underwent histological sectioning and staining with Masson trichrome and toluidine blue. The femoral ACL insertion, QTB graft, and BPTB graft were microscopically analyzed. The width of the direct insertion, thickness of the uncalcified fibrocartilage and calcified fibrocartilage, ligament attachment angle, and cGBA for each group were measured. Eighteen patients who underwent ACL reconstruction with QTB or BPTB autograft were included for the evaluation of GBA using computed tomography images at 1 week postoperatively.
Results:
The mean insertion widths of the femoral ACL, QTB, and BPTB were 7.81, 9.07, and 6.54 mm, respectively. The QTB was 16% wider than the ACL, while the BPTB was 16% narrower than the ACL. The mean insertion thicknesses of the femoral ACL, QTB, and BPTB were 0.53, 0.94, and 0.38 mm, respectively. The QTB was 77% thicker than the ACL (P < .001), while the BPTB was 28% thinner than the ACL (P = .017). The mean ligament attachment angles of the femoral ACL, QTB, and BPTB were 20.3°, 30.2°, and 33.3°, respectively, and the QTB and the BPTB were 49% and 64% larger, respectively, than the ACL. The mean cGBAs of the femoral ACL, QTB, and BPTB were 33.9°, 35.1°, and 12.3°, respectively. The BPTB was 64% smaller than the ACL, while there was no significant difference between the QTB and the ACL. The mean GBA was 57.7°.
Conclusion:
The insertion width and thickness were significantly greater and smaller in the QTB and BPTB grafts, respectively, than in the ACL. The relationship between GBA after ACL reconstruction and cGBA in knee extension indicates that at the femoral tunnel aperture, the BPTB can bend more than the QTB.
Clinical Relevance:
QTB graft may allow more anatomic ACL reconstruction to be performed.
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