Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Korean patients and family members.

COL6A1 and BMP-2 genes have been implicated in ossification of the posterior longitudinal ligament (OPLL) susceptibility in Japanese and Chinese Han populations. However, no study has yet investigated the DNA of unaffected family members of patients with OPLL. This study investigated differences in genetic polymorphisms of BMP-2 and COL6A1 between Korean patients with OPLL and their family members (with and without OPLL). A total of 321 subjects (110 patients with OPLL and 211 family members) were enrolled in the study. Associations between two single nucleotide polymorphisms (SNPs) of the BMP-2 gene (Ser37Ala and Ser87Ser) and two SNPs of COL6A1 [promoter (-572) and intron 33 (+20)] with susceptibility to OPLL of the cervical spine were investigated between the two groups (OPLL+ and OPLL-). Of the 321 subjects, 162 had cervical OPLL (50.4%; 110 patients, 52 family members). There was a familial tendency of OPLL in 34 of the 110 families (30.9%). Allele and haplotype frequencies of the four SNPs in the BMP-2 and COL6A1 genes did not differ significantly between the OPLL+ and OPLL- groups, even when excluding participants over 50 years of age. This is the first report identifying SNPs of COL6A1 and BMP-2 in Korean patients and family members with OPLL. Although allele and haplotype frequencies were similar with those of a previous study in Japanese and Chinese patients, unaffected family members also showed similar rates of these SNPs in the present study. These results suggest that these SNPs may not directly influence the expression of OPLL.

Molecular response of human cervical and lumbar nucleus pulposus cells from degenerated discs following cytokine treatment.

We investigated the molecular response of degenerated human cervical and lumbar nucleus pulposus (NP) cells following cytokine treatment. Degenerated cervical and lumbar discs (8 each) were obtained from patients who underwent discectomy for degenerative disc disease; NP cells were isolated and cultured. The mRNA expressions of aggrecan, alkaline phosphatase, type I collagen, type II collagen, osteocalcin, and Sox9 in the 2 groups were compared by real-time PCR, before and following treatment with rhBMP-2 and TGF-ß1. Immunoreactivity was analyzed to check protein activity. Type I collagen expression was significantly higher in cervical compared with that in lumbar disc cells. The mRNA expression was significantly increased after rhBMP-2 and TGF-ß1 treatment. After rhBMP-2 treatment, mRNA expression of type I and II collagens increased significantly more in cervical than in lumbar NP cells. Following TGF-ß1 treatment, the increase in mRNA expression was not significantly different between cervical and lumbar disc cells. Protein immunoreactivity, before and after cytokine treatment was similar to mRNA expression data. The matrix-related gene expression of cervical and lumbar NP after rhBMP-2 and TGF-ß1 treatment increased similarly, with the exception of collagen expression.

Association of transforming growth factor-beta 1 gene polymorphism with genetic susceptibility to ossification of the posterior longitudinal ligament in Korean patients.

Ossification of the posterior longitudinal ligaments (OPLL) has been considered to be associated with abnormalities of bone metabolism, and transforming growth factor-ß1 (TGF-ß1) has been demonstrated to affect the bone remodeling process. We investigated two SNPs of the TGF-ß1 promoter (-509C>T; rs1800469) and exon 1 (869T>C; rs1982073) in 298 Koreans (98 patients with OPLL and 200 control subjects). The promoter SNP -509C>T was determined by PCR and RFLP, and the TaqMan probe assay was used to determine 869T>C polymorphism genotypes. The subjects were divided into OPLL continuous group (continuous type plus mixed type) and OPLL segmental group (segmental and localized type). We also separately analyzed this association according to gender difference. There was no significant difference in genotype distributions of -509C>T and 869T>C polymorphisms of the TGF-ß1 gene between OPLL patients and controls. A combined analysis of TGF-ß1 -509C>T and 869T>C polymorphisms showed no significant association with OPLL, and a subgroup analysis did not show any significant correlation between the SNP -509C>T or SNP 869T>C and OPLL subgroups. Stratification by gender demonstrated no significant effect. We conclude that promoter region (-509C>T) and exon 1 (869T>C) polymorphisms are not associated with OPLL in the Korean population.

What is the importance of "halo" phenomenon around bone cement following vertebral augmentation for osteoporotic compression fracture?

UNLABELLED: We investigated the importance, risk factors, and clinical course of the radiolucent "halo" phenomenon around bone cement following vertebral augmentation for osteoporotic compression fracture. Preoperative osteonecrosis and a lump cement pattern were the most important risk factors for the peri-cement halo phenomenon, and it was associated with vertebral recollapse. INTRODUCTION: We observed a newly developed radiolucent area around the bone cement following vertebral augmentation for osteoporotic compression fractures. Here, we describe the importance of the peri-cement halo phenomenon, as well as any associated risk factors and long-term sequelae. METHODS: In total, 175 patients (202 treated vertebrae) were enrolled in this study. The treated vertebrae were subdivided into two groups: Group A (with halo, n = 32) and Group B (without halo, n = 170), and the groups were compared with respect to multiple preoperative (age, sex, BMD, preoperative osteonecrosis) and perioperative factors (operative approach: vertebroplasty or kyphoplasty; cement distribution pattern; cement leakage; cement volume), and postoperative results (VAS score, recollapse). Logistic regression analysis was used to evaluate the relationship between the incidence of the peri-cement halo and all of the parameters described above. RESULTS: Rates of osteonecrosis were also significantly higher in Group A than in Group B (62.5% vs. 31.2%, p < 0.05), and kyphoplasty (KP) was performed more frequently in Group A (43.8% vs. 17.6%, p < 0.05). Lump cement (93.8% vs. 30.6%, p < 0.05) and recollapse (78.1% vs. 24.7%, p < 0.05) were also more common among individuals in Group A. Logistic regression analysis also showed that preoperative osteonecrosis (OR = 3.679; 95% CI = 1.677-8.073; p = 0.001), KP (OR = 3.630; 95% CI = 1.628-8.095; p = 0.002), lump pattern (OR = 13.870; 95% CI = 2.907-66.188; p = 0.001), and vertebral recollapse (OR = 5.356; 95% CI = 1.897-15.122; p = 0.002) were significantly associated with peri-cement halo. CONCLUSIONS: The peri-cement halo was found to be associated with vertebral recollapse, this sign likely represents a poor prognostic factor after vertebral augmentation for osteoporotic compression fractures.

Morphological changes of injected calcium phosphate cement in osteoporotic compressed vertebral bodies.

SUMMARY: This study was undertaken to investigate the radiologic and clinical outcomes of vertebroplasty with calcium phosphate (CaP) cement in patients with osteoporotic vertebral compression fractures. The morphological changes of injected CaP cement in osteoporotic compressed vertebral bodies were variable and unpredictable. We suggest that the practice of vertebroplasty using CaP should be reconsidered. INTRODUCTION: Recently, CaP, an osteoconductive filler material, has been used in the treatment of osteoporotic compression fractures. However, the clinical results of CaP-cement-augmented vertebrae are still not well established. The purpose of this study is to assess the clinical results of vertebroplasty with CaP by evaluating the morphological changes of CaP cement in compressed vertebral bodies. METHODS: Fourteen patients have been followed for more than 2 years after vertebroplasty. The following parameters were reviewed: age, sex, T score, compliance with osteoporosis medications, visual analog scale score, compression ratio, subsequent compression fractures, and any morphological changes in the filler material. RESULTS: The morphological changes of injected CaP included reabsorption, condensation, bone formation (osteogenesis), fracture of the CaP solid hump, and heterotopic ossification. Out of 14 patients, 11 (78.6%) developed progression of the compression of the CaP-augmented vertebral bodies after vertebroplasty. CONCLUSIONS: The morphological changes of the injected CaP cement in the vertebral bodies were variable and unpredictable. The compression of the CaP-augmented vertebrae progressed continuously for 2 years or more. The findings of this study suggest that vertebroplasty using CaP cement should be reconsidered.

Recollapse of previous vertebral compression fracture after percutaneous vertebroplasty.

UNLABELLED: This study was undertaken to investigate the incidence rate, characteristics, and predisposing factors associated with recollapse of the same vertebrae after percutaneous vertebroplasty (PVP). Recollapse of the same vertebra after PVP is the one of the complications of the procedure, and the incidence rate in our study was 3.21%. The most important predisposing factor was pre-operative osteonecrosis. Recollapse was not related to trauma. INTRODUCTION: PVP using polymethylmethacrylate has become a popular treatment for osteoporotic vertebral compression fracture. Recollapse of the same vertebrae after PVP has rarely been reported. This study was undertaken to investigate the incidence, characteristics, and predisposing factors associated with recollapse of the same vertebrae after PVP. METHODS: Eleven patients (seven females and four males; mean age, 69.91 +/- 5.49 years), out of a total of 343 patients, developed recollapse of the same vertebra after PVP. The 11 patients who developed recollapse comprised the "recollapse group", while the remaining 332 patients comprised the "well-maintained group". RESULTS: Pre-operative magnetic resonance imaging revealed that the incidence of osteonecrosis was significantly higher in the recollapse group than the well-maintained group (p < 0.05). The degree of re-expansion of the compressed vertebral body after PVP was significantly higher in the recollapse group than in the well-maintained group (p < 0.05). CONCLUSIONS: The most important predisposing factor for recollapse was pre-operative osteonecrosis. Recollapse was not related to trauma. Osteoporotic vertebral compression fracture with osteonecrosis or pseudoarthrosis has been regarded as a relative indication for PVP; however, the findings of this study suggest that this disease category may be a relative contraindication for PVP.

The AdLMP-1 transfection in two different cells; AF cells, chondrocytes as potential cell therapy candidates for disc degeneration.

BACKGROUND: LMP-1 is known to increase proteoglycan production through the upregulating the BMPs and it is also known that BMP-2 acts on anulus fibrosus cells and chondrocytes to increase proteoglycan production. METHOD: We carried out an experiment, the effect of AdLMP-1 transfection on AF cells and chondrocytes in the production of sulfated-glycosaminoglycans, mRNA expression (aggrecan, type I, II collagen, LMP-1, BMP-2, and BMP-7), and immunofluorescence staining. AF cells and chondrocytes were grown in monolayer and treated for 6 days with AdLMP1-green fluorescence protein (GFP) (10, 20, and 30 multiplicity of infection [MOI]). After 6 days, the sGAG content in the media was quantified using 1,9-dimethylmethylene blue staining. The mRNA expression was measured with real-time PCR after 20 MOI infection of AdLMP1-GFP. The each cells treated with 20 MOI infection of AdGFP was used as a control group for the mRNA expression. The each cell group was immunofluorescence stained with each antibodies in the chamber slide at 3 x 10(4) cells/chamber. FINDINGS: 1) The sGAG production was maximum in 20 MOI AdLMP1-GFP infection on the AdLMP-1 treatment for both of AF cells and chondrocytes. 2) The mRNA expression of aggrecan, type I collagen, type II collagen, LMP-1, BMP-2, and BMP-7 is increased in both AF cells and chondrocytes in 20 MOI AdLMP1-GFP infection. 3) On the immunofluorescence staining results, the positive immunofluorescence stained cell numbers are increased after 20 MOI AdLMP1-GFP infection concordant with upregulation of mRNA expression. CONCLUSIONS: The AdLMP-1 treatments in AF cells and chondrocytes may be useful for cell transplantation therapy in disc degeneration.

Prevalence of osteoporosis in patients requiring spine surgery: incidence and significance of osteoporosis in spine disease.

UNLABELLED: The purpose of this study is to evaluate the incidence of osteoporosis in patients requiring spine surgery. Among patients older than 50 years, the rate of osteoporosis in males was 14.5% and the rate osteoporosis in females was 51.3%. We strongly recommend an evaluation and treatment for osteoporosis in the patients requiring spine surgery, especially in females over 50 years old. INTRODUCTION: Because lifespan is increasing, there is an increase in the incidence of osteoporosis in elderly spine surgery patients. The osteoporosis may adversely influence the fusion rate and the surgical outcome. The purpose of this study is to evaluate the incidence of osteoporosis in patients requiring spine surgery. METHODS: A total of 1,321 patients underwent spine surgeries at our institute from January 1, 2005 to December 31, 2005. Among them, there were 562 patients (42.5%) younger than 50 years old, and 759 patients (57.6%) older than 50 years old. Prior to operation, we evaluated the patients for osteoporosis on both the femur head and lumbar spine by measuring the bone mineral density (BMD) by the dual-energy X-ray absorptiometry (DXA). Based on the World Health Organization (WHO) criteria for osteoporosis, we chose the T-score to determine normal (>-1), osteopenia (-1>or=, >-2.5), and osteoporosis (

Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat.

There have been many efforts to recover neuronal function from spinal cord injuries, but there are some limitations in the treatment of spinal cord injuries. The neural stem cell has been noted for its pluripotency to differentiate into various neural cell types. The human umbilical cord blood cells (HUCBs) are more pluripotent and genetically flexible than bone marrow neural stem cells. The HUCBs could be more frequently used for spinal cord injury treatment in the future. Moderate degree spinal cord injured rats were classified into 3 subgroups, group A: media was injected into the cord injury site, group B: HUCBs were transplanted into the cord injury site, and group C: HUCBs with BDNF (Brain-derived neutrophic factor) were transplanted into the cord injury site. We checked the BBB scores to evaluate the functional recovery in each group at 8 weeks after transplantation. We then, finally checked the neural cell differentiation with double immunofluorescence staining, and we also analyzed the axonal regeneration with retrograde labelling of brain stem neurons by using fluorogold. The HUCBs transplanted group improved, more than the control group at every week after transplantation, and also, the BDNF enabled an improvement of the BBB locomotion scores since the 1 week after its application (P<0.05). 8 weeks after transplantation, the HUCBs with BDNF transplanted group had more greatly improved BBB scores, than the other groups (P<0.001). The transplanted HUCBs were differentiated into various neural cells, which were confirmed by double immunofluorescence staining of BrdU and GFAP & MAP-2 staining. The HUCBs and BDNF each have individual positive effects on axonal regeneration. The HUCBs can differentiate into neural cells and induce motor function improvement in the cord injured rat models. Especially, the BDNF has effectiveness for neurological function improvement due to axonal regeneration in the early cord injury stage. Thus the HUCBs and BDNF have recovery effects of a moderate degree for cord injured rats.