The effect of ultraviolet photofunctionalization of titanium instrumentation in lumbar fusion: a non-randomized controlled trial.

BACKGROUND: Titanium instrumentations are widely used in orthopedics; the metal bonds with bone in a process called osseointegration. Over time, hydrocarbons adhere to the instrumentation, which weakens the bone-binding ability. Ultraviolet photofunctionalization enhances the bone-binding ability of instrumentation by reducing hydrocarbons. The process has been proven effective in dentistry, but its effects in orthopedics are unverified. We aimed to determine the effect of ultraviolet photofunctionalization of titanium instrumentation used in lumbar fusion. METHODS: This was a non-randomized controlled trial. We prospectively enrolled 13 patients who underwent lumbar fusion surgery. We inserted two pure titanium cages into each intervertebral space; one cage had undergone ultraviolet photofunctionalization, while the other was untreated. The degree of osteosclerosis around both cages was then compared by measuring the densities around the cages on imaging at 2, 3, 6, and 12 months postoperatively compared with 1 month postoperatively. The carbon attachment of the titanium cages was measured using X-ray photoelectron spectroscopy. RESULTS: There was no significant difference between the degree of osteosclerosis (as assessed by the density) around the treated versus untreated cages at any timepoint. The ratio of carbon attachment of the titanium cages was only 20%, which was markedly less than the ratio of carbon attachment to titanium instrumentation previously reported in the dentistry field. CONCLUSIONS: The effect of ultraviolet photofunctionalization of titanium instrumentation in spine surgery is questionable at present. The biological aging of the titanium may be affected by differences in the manufacturing process of orthopedics instrumentation versus dentistry instrumentation. TRIAL REGISTRATION: UMIN Clinical Trials Registry (Identifier: UMIN000014103 ; retrospectively registered on June 1, 2014).

TGF-ß signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells.

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-ß (TGF-ß) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells compared with C28/I2 normal chondrocytes, while TGF-ß1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-ß signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-ß and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-ß signalling are mutually inhibitory in chondrosarcoma cells.

Osteoarthritis of the hip joint in elderly patients is most commonly atrophic, with low parameters of acetabular dysplasia and possible involvement of osteoporosis.

As elderly patients with hip osteoarthritis aged, acetabular dysplasia parameters decreased (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) and the incidence of the atrophic type increased. Vertebral body fracture was more frequent in the atrophic type, suggesting the involvement of osteoporosis at the onset of hip osteoarthritis. INTRODUCTION: Osteoarthritis (OA) is associated with increased bone formation at a local site. However, excessive bone resorption has also been found to occur in the early stages of OA. Osteoporosis may be involved in the onset of OA in elderly patients. We conducted a cross-sectional radiographic study of patients with hip OA and examined the association between age and factors of acetabular dysplasia (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) as well as the osteoblastic response to determine the potential involvement of osteoporosis. METHODS: This study included 366 patients (58 men, 308 women) who had undergone total hip arthroplasty for the diagnosis of hip OA. We measured the parameters of acetabular dysplasia using preoperative frontal X-ray images and evaluated each patient according to Bombelli classification of OA (hypertrophic, normotrophic, or atrophic type). RESULTS: As the patients aged, the parameters of acetabular dysplasia decreased. The incidence of the atrophic type of OA was significantly higher in older patients. Vertebral body fractures were more frequent in the atrophic type than in the other types. Additionally, the index of acetabular dysplasia was lower in the atrophic type. By contrast, the hypertrophic type was present in relatively younger patients and was associated with an increased index of acetabular dysplasia. CONCLUSION: In elderly patients with hip OA, the parameters of acetabular dysplasia decreased and the incidence of the atrophic type increased as the patients aged. The frequency of vertebral body fracture was high in patients with the atrophic type, suggesting the involvement of osteoporosis in the onset of hip OA.

Finite element analysis of cementless femoral stems based on mid- and long-term radiological evaluation.

BACKGROUND: Femoral bone remodeling in response to stress shielding induces periprosthetic bone loss. Computerized finite element analysis (FEA) is employed to demonstrate differences in initial stress distribution. However, FEA is often performed without considering the precise sites at which the stem was fixed. We determined whether FEA reflects mid-term radiological examination exactly as predicted following long-term stress shielding. METHODS: Femur-stem fixation sites were evaluated radiologically according to the location of spot welds in two anatomical cementless stem designs. Based on mid-term radiological results, four femur-stem bonding site conditions were defined as: (Condition A) no bonding; (Condition B) bonding within the 10 mm area proximal to the distal border of the porous area; (Condition C) bonding of the entire porous area; and (Condition D) bonding of the entire femoral stem, prior to conducting FEA analysis. Furthermore, we radiographically evaluated mid- and long-term stress shielding, and measured bone mineral density of the femur 10 years after total hip arthroplasty. RESULTS: Spot welds appeared frequently around the border between the porous and smooth areas. FEA showed that, based on mid-term radiological evaluation, von Mises stress was reduced in condition B in the area proximal to the femur-stem bonding sites for both stem designs compared with condition A (no bonding). Conversely, von Mises stress at all areas of the femur-stem bonding sites in conditions C and D was higher than that in condition A. With respect to stress shielding progression, there was no significant difference between the two types of stem designs. However, stress shielding progressed and was significantly higher in the presence of spot welds (p = 0.001). In both stem designs, bone mineral density in zone VII was significantly lower than that in the contralateral hips. CONCLUSIONS: These results indicate that FEA based on mid-term radiological evaluation may be helpful to predict the influence of long-term stress shielding more precisely.

Endemic impact of human T cell leukemia virus type 1 screening in bone allografts.

Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service. Between 2008 and 2012, we collected 282 femoral heads at the Kagoshima regional bone bank from living donors with osteoarthritis of the hip joint. Among the 282 candidate donors, 32 donors (11.3 %) were seropositive for anti-HTLV-1 antibody; notably, this prevalence is higher than that reported for blood donors in this area. Additionally, to determine if HTLV-1 genes are detectable after processing, we examined the bone marrow of the femoral heads from seropositive donors by conducting PCR assays. Our results confirm the existence of viral genes following the heat treatment processing of the femoral heads. Therefore, it is important to inactivate a virus completely by heat-treatment. Together, our findings highlight the importance of HTLV-1 screening at bone banks, particularly in HTLV-1-endemic areas such as southwest Japan.

Retro-odontoid mass without atlantoaxial instability causing cervical myelopathy: a case report of transdural surgical resection.

INTRODUCTION: Retro-odontoid mass rarely occur in patients with noninflammatory retro-odontoid lesions without atlantoaxial instability. We describe a rare case of retro-odontoid mass without atlantoaxial instability operated on by a transdural approach. CASE PRESENTATION: The patient was an 83-year-old man who presented with a retro-odontoid mass causing symptomatic cervical myelopathy. Preoperative magnetic resonance imaging (MRI) revealed that the mass was severely compressing the spinal cord. We operated on it via a C1 laminectomy and performed tumor resection by a transdural approach. Pathological findings from the operative specimen confirmed the diagnosis; histopathological examination revealed that the mass contained fibrinoid material, and collagenous tissue with myxoid changes, but no granulation or a granulomatous lesion. Postoperative MRI confirmed spinal cord decompression. The patient's symptoms were alleviated, and he has not had a recurrence or cervical instability in the 7 years since his surgery. DISCUSSION: We successfully used a transdural approach in the present case and have observed no recurrence for 7 years postoperatively. C1 laminectomy is reportedly beneficial, especially for elderly patients, given the risk of other surgical options using an anterior transoral approach or posterior fusion. However, most tumors do not attenuate after C1 laminectomy alone; hence, we think that tumor resection by the transdural approach is one effective method to perform enucleation of the tumor after C1 laminectomy.

Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

Bone morphogenic protein (BMP) signaling up-regulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt protein signaling pathway as a negative feedback mechanism.

Although bone morphogenic protein (BMP) signaling promotes chondrogenesis, it is not clear whether BMP-induced chondrocyte maturation is cell-autonomously terminated. Loss of function of Smpd3 in mice results in an increase in mature hypertrophic chondrocytes. Here, we report that in chondrocytes the Runx2-dependent expression of Smpd3 was increased by BMP-2 stimulation. Neutral sphingomyelinase 2 (nSMase2), encoded by the Smpd3 gene, was detected both in prehypertrophic and hypertrophic chondrocytes of mouse embryo bone cartilage. An siRNA for Smpd3, as well as the nSMase inhibitor GW4869, significantly enhanced BMP-2-induced differentiation and maturation of chondrocytes. Conversely, overexpression of Smpd3 or C2-ceramide, which mimics the function of nSMase2, inhibited chondrogenesis. Upon induction of Smpd3 siRNA or GW4869, phosphorylation of both Akt and S6 proteins was increased. The accelerated chondrogenesis induced by Smpd3 silencing was negated by application of the Akt inhibitor MK2206 or the mammalian target of rapamycin inhibitor rapamycin. Importantly, in mouse bone culture, GW4869 treatment significantly promoted BMP-2-induced hypertrophic maturation and calcification of chondrocytes, which subsequently was eliminated by C2-ceramide. Smpd3 knockdown decreased the apoptosis of terminally matured ATDC5 chondrocytes, probably as a result of decreased ceramide production. In addition, we found that expression of hyaluronan synthase 2 (Has2) was elevated by a loss of Smpd3, which was restored by MK2206. Indeed, expression of Has2 protein decreased in nSMase2-positive hypertrophic chondrocytes in the bones of mouse embryos. Our data suggest that the Smpd3/nSMase2-ceramide-Akt signaling axis negatively regulates BMP-induced chondrocyte maturation and Has2 expression to control the rate of endochondral ossification as a negative feedback mechanism.