Background: It is not clear how BMP-induced chondrocyte maturation is cell-autonomously terminated. Results: BMP-2 induced the ceramide-generating enzyme neutral sphingomyelinase 2 (nSMase2) in chondrocytes, whereas silencing of nSMase2 enhanced maturation in an Akt signaling-dependent manner. Conclusion: nSMase2 signaling regulates BMP-induced chondrocyte maturation as a negative feedback mechanism. Significance: This study elucidated the novel link between BMP and lipid signaling in chondrogenesis.

Background:The mechanisms by which Hivep3 regulates the osteochondrogenesis remain elusive. Results: Knockdown of Hivep3 down-regulated Alg2 expression. Alg2 suppressed osteoblast differentiation by inhibiting the activity of Runx2. Alg2 silencing suppressed the expression of Creb3l2 and chondrogenesis. Conclusion: Alg2 may be a modulator of osteochondrogenesis. Significance: This is the first report to describe the association of an Alg gene with osteochondrogenesis.

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) 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-β1 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-β signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-β 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-β signalling are mutually inhibitory in chondrosarcoma cells.

SummaryAs 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.IntroductionOsteoarthritis (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.MethodsThis 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).ResultsAs 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.ConclusionIn 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.

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).