transforming-growth-factor-beta and Spinal-Fractures

The study of primary hip OA is continuing to redefine what was once considered a stagnant pathology as one of dynamic change, occurring over a long period of time involving the many composite tissue types of the joint including the bone. Examination of the inverse relationships evident between OA and fracture cohorts, including individuals with osteoporosis (OP), indicates an imbalance in formation and resorption in the bony component of both pathologies. This review contains an overview of primary OA followed by an assessment of differential gene expression and altered cellular characteristics identified in the bony compartments of primary hip OA, with a focus on the wingless mouse mammary tumor virus integration (Wnt) and TGF-β signalling pathways. The studies reviewed here suggest that OA is a systemic disease involving the bone and validate the assessment of molecular changes to further investigate this complex disease.

Topics: Animals; Biomarkers; Bone Remodeling; Cell Proliferation; Gene Expression; Hip Fractures; Humans; Mice; Osteoarthritis, Hip; Osteoblasts; Rats; Risk Factors; Signal Transduction; Spinal Fractures; Transforming Growth Factor beta; Wnt Proteins

Associations between genes and diseases manifest as the influence of gene expression on disease development as well as the impact of variations in the disease-related genes themselves. It's important to determine the genetic variations that can lead to compressed fractures of osteoporotic, thoracic lumbar vertebrae to develop personalized clinical methods to prevent or delay the disease's development.. The study intended to explore the correlations between the gene polymorphisms and gene expressions of the interleukin-6 (IL-6) gene and the transforming growth factor-beta (TGF-β) gene and osteoporotic, thoracolumbar, vertebral compression fracture.. The research team performed an observational study using data from medical records.. The study took place at Xuzhou Medical University in Xuzhou, China.. Participants were 200 patients with an osteoporotic, thoracolumbar, vertebral compression fracture who had been admitted to the hospital at the university between 2019 and 2021 prior to the study and 200 healthy people The research team divided the participants into two groups. The patients became participants in the disease group, and the healthy individuals became participants in the control group.. The research team: (1) collected peripheral blood from the two groups, (2) extracted genomic deoxyribonucleic acids (DNAs) from karyocytes, (3) examined the IL-6 and TGF-β gene polymorphisms, and (4) analyzed and correlated participants' clinical data with the gene polymorphisms and expressions. The team used a quantitative polymerase chain reaction (qPCR) to examine the expression levels of IL-6 and TGF-β.. Compared to the control group, the disease group: (1) had allele distributions that were significantly different at the rs2069829 locus of the IL-6 gene (P < .001) and at the rs3087453 of the TGF-β gene (P = .004); (2) had significantly higher frequencies of allele T at the rs2069829 locus of the IL-6 gene and of allele G at the rs3087453 locus of the TGF-β gene; (3) had genotype distributions that were significantly different at the rs2069829 locus (P < .001) and the rs2069857 locus (P = .048) of the IL-6 gene and at the rs3087453 locus (P < .001) of the TGF-β gene; (4) had frequencies that were significantly higher of the TT genotype at the rs2069829 locus, the CC genotype at the rs2069857 locus, and the GC genotype at the rs3087453 locus of the IL-6 gene and the TGF-β gene; (5) had dominant models that were significantly different at the rs2069829 locus of the IL-6 gene (P = .009) and at rs3087453 locus of the TGF-β gene (P = .026) and had a recessive model that was significantly different at the rs2069857 locus of the IL-6 gene (P = .040); (6) had significantly different haplotypes CC (P < .001) and TC (P < .001) at the rs2069829 locus and the rs2069857 locus of the IL-6 gene and a significantly different haplotype AC (P = .011) at the rs1800469 locus and the rs3087453 locus of the TGF-β gene; (7) had an IL-6 gene polymorphism at the rs2069857 locus that was related to the expression of the IL-6 gene (P < .05) and an expression of the IL-6 gene for participants with the AA genotype that was significantly lower than for other genotypes; (8) had a TGF-β gene polymorphism at the rs1800469 locus that was associated with the expression of the TGF-β gene (P < .05), and an expression for participants with the GG genotype that was significantly higher than for other genotypes; (9) had an IL-6 gene polymorphism at the rs2069857 locus with an overt correlation with the genotype of osteoporotic, thoracolumbar, vertebral compression fracture (P < .001). Also, participants in the disease group with the genotype CC mainly had type 2 and 3 fractures, while those with genotype AA primarily had type 0 and 1 fractures.. IL-6 and TGF-β gene polymorphisms and expressions are significantly related to osteoporotic, thoracolumbar, vertebral compression fracture.

Topics: Fractures, Compression; Gene Frequency; Humans; Interleukin-6; Lumbar Vertebrae; Osteoporotic Fractures; Polymorphism, Genetic; Spinal Fractures; Thoracic Vertebrae; Transforming Growth Factor beta

Current national patterns as a function of patient-, hospital-, and procedure-related factors, and complication rates in the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an adjunct to the practice of pediatric spine surgery have scarcely been investigated.. The authors conducted a cross-sectional study using data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. Univariate and multivariate logistic regression were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals, and p values < 0.05 were considered to be statistically significant.. The authors identified 9538 hospitalizations in pediatric patients 20 years old or younger who had undergone spinal fusion in the US in 2009; 1541 of these admissions were associated with rhBMP-2 use. By multivariate logistic regression, the following factors were associated with rhBMP-2 use: patient age 15-20 years; length of hospital stay (adjusted odds ratio [aOR] 1.01, p = 0.017); insurance status (private [aOR 1.49, p < 0.001] compared with Medicaid); hospital type (nonchildren's hospital); region (Midwest [aOR 2.49, p = 0.008] compared with Northeast); spinal refusion (aOR 2.20, p < 0.001); spinal fusion approach/segment (anterior lumbar [aOR 1.73, p < 0.001] and occipitocervical [aOR 1.86, p = 0.013] compared with posterior lumbar); short segment length (aOR 1.42, p = 0.016) and midlength (aOR 1.44, p = 0.005) compared with long; and preoperative diagnosis (Scheuermann kyphosis [aOR 1.56, p < 0.017] and spondylolisthesis [aOR 1.93, p < 0.001]).. Use of BMP in pediatric spine procedures now comprises more than 10% of pediatric spinal fusion. Patient-related (age, insurance type, diagnosis); hospital-related (children's hospital vs general hospital, region in the US); and procedure-related (redo fusion, anterior vs posterior approach, spinal levels, number of levels fused) factors are associated with the variation in BMP use in the US.

Topics: Adolescent; Bone Morphogenetic Protein 2; Cervical Vertebrae; Cross-Sectional Studies; Female; Humans; Length of Stay; Logistic Models; Lumbar Vertebrae; Male; Odds Ratio; Practice Patterns, Physicians'; Recombinant Proteins; Reoperation; Spinal Curvatures; Spinal Fractures; Spinal Fusion; Spine; Spondylolisthesis; Thoracic Vertebrae; Transforming Growth Factor beta; United States; Young Adult

A histologic study of recombinant human bone morphogenetic protein-2/calcium phosphate cement (rhBMP-2/CPC) using adult rhesus monkeys in vivo.. To evaluate the histologic changes of rhBMP-2/CPC in vertebroplasty and determine the feasibility of this bone substitution instead of polymethylmethacrylate (PMMA).. Previous studies have shown that the new rhBMP-2/nanoscale CPC has a suitable strength and injection for vertebroplasty. However, the osteoinductive properties and biodegradable characteristics are still unclear.. Percutaneous vertebroplasty (PVP) was performed in 4 adult rhesus monkeys of 2 groups. Ten vertebral bodies (VBs) from T10-L7 of each rhesus were selected, and the 20 VBs in each group were randomly divided into 3 subgroups. Subgroup A (rhBMP-2/CPC): 8 VBs, filled with rhBMP-2/CPC; Subgroup B (PMMA): 6 VBs, filled with injectable PMMA; Subgroup C (control): 6 VBs, filled with normal saline. The 2 rhesus monkeys from each of the groups were killed at 2 and 6 months after operation, respectively. Individual specimens from the 40 VBs were collected for histologic observation.. In subgroup A, radiographic and histologic observations showed that the part of the rhBMP-2/CPC cement degraded with new bone and new vessel ingrowths, into the material, after 2 months. In addition, gaps, fibrous hyperplasia, or sclerotic callus were not found in the interface. After 6 months, the cement was nearly all replaced by mature bone tissue. In subgroup B, the inflammatory cell infiltration and fibrous membrane gapping were found after 2 months, and subsided partly at 6 months. But no new bone formation and material degradation were discovered. In subgroup C, the tunnels were filled with irregular new trabeculae after 2 months and unrecognizable from the surrounding mature bone after 6 months.. It is confirmed that the rhBMP-2/CPC is an osteoinductive and biodegradable material (in animal trials). It may also be an alternative to PMMA in order to achieve biostabilization in a vertebroplasty.

Topics: Animals; Biocompatible Materials; Bone Cements; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Humans; Injections; Lumbar Vertebrae; Macaca mulatta; Polymethyl Methacrylate; Random Allocation; Recombinant Proteins; Spinal Fractures; Thoracic Vertebrae; Transforming Growth Factor beta; Vertebroplasty

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a genetically engineered protein which recruits bone-forming cells to the surgical area and converts local cells to bone. In clinical studies, rhBMP-2 successfully enhanced anterior/posterior spinal fusions in adult humans without bone grafts. Efficacy in paediatric spinal fusion is not yet reported.. We describe the surgical technique and results in a 2-year-old girl with unstable C1-2 cervical spine injury who underwent non-metal-instrumented C1/C2 posterior spinal fusion using rhBMP-2 applied to an absorbable collagen sponge (ACS) matrix.. Radiologically verifiable bony fusion began at 3 weeks. Within 8 weeks solid C1-C2 spinal fusion was confirmed by CT scan. There was no evidence of spinal canal encroachment and no adverse effects related to the rhBMP-2/ACS-carrier matrix.. rhBMP-2 enhanced posterior cervical fusion at an impressive rate in a very young child. This finding is encouraging both to effectiveness and speed. However, with all new developments, we highlight the need for further experience and longer follow-up in children.

Topics: Age Factors; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Child, Preschool; Female; Humans; Recombinant Proteins; Spinal Fractures; Spinal Fusion; Transforming Growth Factor beta

Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects. We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n=10) and those without (n=15), and also a control group with an isolated fracture of a long bone (n=12). The level of transforming growth factor-beta (TGF-beta), was measured at five time points after injury (days 1, 5, 10, 42 and 84). The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p<0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p

Topics: Acute Disease; Adult; Female; Fracture Healing; Humans; Male; Spinal Cord Injuries; Spinal Fractures; Time Factors; Transforming Growth Factor beta

Molecular study of gene expression in rabbit lumbar pseudarthrosis repairs using reverse transcriptase polymerase chain reaction.. To evaluate differential gene expression of no graft, autograft, and osteogenic protein-1 treated pseudarthroses.. Osteogenic protein-1 is a potential bone graft alternative that has achieved high fusion rates in a rabbit lumbar fusion model, including in the repair of nicotine-induced pseudarthroses. A previous study established a correlation between osteogenic protein-1 fusion outcomes and an enhanced level of cytokine gene expression. The expression of such cytokines is known to be decreased in nicotine-exposed rabbit fusion masses.. Messenger ribonucleic acid was isolated from nicotine-exposed New Zealand white rabbit lumbar pseudarthroses following attempted no graft, autograft, and osteogenic protein-1 pseudarthrosis repairs. Reverse transcriptase polymerase chain reaction was used to assess the expression of angiogenin, angiopoietin, intercellular adhesion molecule, platelet-derived growth factor-beta, vascular endothelial growth factor, bone morphogenetic proteins 2 and 7, type I collagen, and osteonectin. Glyceraldehyde-3-phosphate dehydrogenase was used as a constitutively expressed control.. Levels of gene expression in the osteogenic protein-1 group were higher than those of the autograft group, which were higher than the no graft group for the majority of the genes studied.. In the rabbit pseudarthrosis model, gene expression data supported the hypothesis that successful pseudarthrosis repair is related to the induction of osteogenic and angiogenic cytokines by osteogenic protein-1.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Gene Expression Regulation; Lumbar Vertebrae; Pseudarthrosis; Rabbits; Spinal Fractures; Spinal Fusion; Transforming Growth Factor beta

Transforming growth factor-beta-1 (TGF-Beta(1)) has been implicated in bone mineral density (BMD) determination. We investigated the relationship between the TGF polymorphism, BMD, and vertebral fractures in 588 Chinese men and women. No association between TGF polymorphism and BMD was observed in postmenopausal women (aged 55-59 years), elderly men (aged 70-79 years), or elderly women (aged 70-79 years) at the hip, spine, or total body ( P >> 0.05 by two-way ANOVA). In all study groups, there was no effect of an interaction between TGF polymorphism and calcium intake on BMD ( P >> 0.05 for the interaction effects by two-way ANOVA). No statistical significant association was observed between TGF polymorphism and vertebral fracture in elderly men or women ( P >> 0.05 by the chi-square test), even though men of the TT and TC genotypes seem to have more vertebral fractures. Contrary to previous studies that found an association between BMD and TGF polymorphism in the Japanese, we found no association between TGF polymorphism and BMD of elderly Chinese men or women. This finding could result from different sampling methods between the previous and current studies and environmental factors and ethnic differences between the two populations.

Topics: Aged; Bone Density; Calcium, Dietary; China; Female; Genotype; Hip; Humans; Male; Middle Aged; Osteoporosis; Polymorphism, Genetic; Radiography; Spinal Fractures; Spine; Statistics as Topic; Transforming Growth Factor beta; Transforming Growth Factor beta1

The study presented here is a pilot study in five patients with unstable thoracolumbar spine fractures treated with transpedicular OP-1 transplantation, short segment instrumentation and posterolateral fusion. Recombinant bone morphogenetic protein-7 in combination with a collagen carrier, also referred to as OP-1, has demonstrated ability to induce healing in long-bone segmental defects in dogs, rabbits and monkeys and to induce successful posterolateral spinal fusion in dogs without need for autogenous bone graft. Furthermore OP-1 has been demonstrated to be effective as a bone graft substitute when performing the PLIF maneuver in a sheep model. Five patients with single-level unstable burst fracture and no neurological impairment were treated with intracorporal OP-1 transplantation, posterior fixation (USS) and posterolateral fusion. One patient with osteomalacia and an L2 burst fracture had an additional intracorporal transplantation performed proximal to the instrumented segment, i.e. OP-1 into T 12 and autogenous bone into T 11. Follow-up time was 12-18 months. On serial radiographs, Cobb and kyphotic angles, as well as anterior, middle and posterior column heights, were measured. Serial CT scans were performed to determine the bone mineral density at fracture level. In one case, radiographic and CT evaluation after 3 and 6 months showed severe resorption at the site of transplantation, but after 12 months, new bone had started to fill in at the area of resorption. In all cases there was loss of correction with regard to anterior and middle column height and sagittal balance at the latest follow-up. These preliminary results regarding OP-1 as a bone graft substitute and stimulator of new bone formation have been disappointing, as the OP-1 device in this study was not capable of inducing an early sufficient structural bone support. There are indications to suggest that OP-1 application to a fracture site in humans might result in detrimental enhanced bone resorption as a primary event.

Topics: Adult; Aged; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Resorption; Female; Humans; Internal Fixators; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Recombinant Proteins; Spinal Fractures; Spinal Fusion; Thoracic Vertebrae; Transforming Growth Factor beta