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ObjectiveThe present study aims to increase the concentration of genetically modified bone marrow mesenchymal stem cells (BMSCs) in the distraction osteogenesis (DO) interstitial space and induce the conversion of BMSCs to osteoblasts to improve the osteogenic efficiency in DO and shorten the treatment period.MethodsBone morphogenetic protein 1 (BMP-1) and green fluorescent protein (GFP) gene-modified cell sheets of BMSCs were constructed by tissue engineering. Thirty-six New Zealand white rabbits were randomly divided into three groups: group A (the blank control group), group B (the GFP group) with the injection of GFP gene-modified BMSC sheets into the DO gap, and group C (the BMP-1 group) with the injection of BMP-1 gene-modified BMSC sheets into the DO gap. Rabbits in all three groups were distracted for 5 days at a distraction rate of 2.0 mm/d, once/day. After distraction, the above-mentioned cell sheet suspension was injected into the distraction gap to observe osteogenesis, which was observed by gross specimen observation, micro-computed tomography (Micro-CT) scanning, and histomorphology.ResultsThe gross specimen observation showed that all animals had smooth and continuous bone cortex in the distraction region with relatively high hardness. The osteogenesis quality or hardness was ranked from the highest to the lowest, as Group C > Group B > Group A. Micro-CT and histomorphological observation revealed that group C had better maturation and bone volume of the new bone in the DO region at weeks 3 and 6 than groups B and A.ConclusionBMP-1 gene-modified BMSC sheets could effectively promote the formation of new bone during rapid DO in the mandible, compensating for the poor osteogenesis caused by rapid distraction and providing a new approach to shorten the DO treatment period in clinical practice.

Tenosynovitis with psammomatous calcification is an extremely rare clinicopathological condition, which is characterized histopathologically by the presence of numerous psammomatous calcifications surrounded by a granulomatous reaction comprising a mixture of histiocytes and fibroblasts. The pathogenesis of this disease remains unclear, although an association with repetitive tendinous injury has been proposed. The present study describes the details of a case in an elderly Japanese female, and, to the best of our knowledge, the first known immunohistochemical analysis of the mechanism underlying psammomatous calcification formation. A 66-year-old Japanese woman presented with pain in the right wrist. The lesion was surgically resected. Histopathological examination revealed a well-circumscribed lesion composed of psammomatous calcification. The calcification was surrounded by histiocytes, and a few multinucleated giant cells and fibroblastic spindle cells. Immunohistochemical study revealed that these histiocytes were positive for cluster of differentiation 163, and the histiocytes and spindle cells surrounding the psammomatous calcification expressed bone morphogenetic protein-1 (BMP-1). Tenosynovitis with psammomatous calcification is hypothesized to be a distinctive subtype of idiopathic calcifying tenosynovitis involving an unusual reactive or degenerative process. BMP-1 has been demonstrated to be involved in the regulation of hard tissue mineralization, and its expression has been suggested to be associated with psammoma formation in papillary thyroid cancer. To the best of our knowledge, the case report within the present study suggested for the first time that BMP-1 expression was associated with development of psammomatous calcification in this condition. [ABSTRACT FROM AUTHOR]

Objective: To observe the expression of serum bone morphogenetic protein-1 (BMP-1) during the process of periodontal bone regeneration and its clinical significance. Methods: 196 cases of patients with periodontal bone defects admitted in our hospital were enrolled in this study, conventional basic periodontal treatment (gingival .Tie governance thoroughly, subgingival scaling cure, leveling the root surface) was used. The Bio-oss artificial bone material and the Bio-gide collagen membrane were implanted while the bone defect was repaired by guided tissue regeneration (GTR). The levels of serum BMP-1 were measured before and after treatment, and the relationship between the expression of BMP-1 and the repair of periodontal bone defects was analyzed. Results: Compared with before treatment, patients with periodontal bone defects were repaired after treatment. The PPD and bone mineral density of all patients were significantly improved (P<0.05) after treatment. The bone mineral density (BMD) decreased significantly after 6 months of treatment, but it was significantly higher than that before treatment (P<0.05). Compared with before treatment, the levels of serum BMP-1 were significantly increased in all patients at 1 day, 2 days, 5 days, 10 days, 1 month. 3 months and 6 months after treatment (P<0.05), and the level of BMP-1 was negatively correlated with PPD (P<0.05). but the correlation with bone mineral density showed no significant difference(P>0. 05). Conclusions: It was found that the dynamic changes of BMP-1 in periodontal bone repair were related to the recovery of periodontal bone. [ABSTRACT FROM AUTHOR]

Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation. ALP activity was measured via histochemical staining and western blotting was used to determine the expression of factors associated with inflammation. C2C12 cells were initially treated with 200 ng/ml bone morphogenetic protein (BMP)-2 alone for 3 days, which caused a significant increase in ALP activity (P<0.01). However, treatment with tumor necrosis factor (TNF)-α significantly decreased the ALP activity (P<0.05). Notably, treatment with the chronic inflammatory cytokine TNF-α significantly decreased the effect of BMP-2 in C2C12 cells compared with BMP-2 treatment alone (P<0.01). C2C12 cells were treated with increasing concentrations of BMP-2 or TNF-α for 3 days. The results demonstrated that TNF-α treatment significantly inhibited BMP-2-induced osteoblast differentiation in a dose-dependent manner (P<0.01). The role of triptolide in BMP-2-induced osteoblast differentiation was also examined. Cells were treated with BMP-2, BMP-2 + TNF-α alone, or BMP2 + TNF-α with increasing concentrations of triptolide (4, 8 or 16 ng/ml). After 3 days, the results of ALP activity revealed that triptolide significantly reversed the TNF-α-associated inhibition of osteoblast differentiation (P<0.01). Western blotting analysis demonstrated that triptolide markedly inhibited the phosphorylation of nuclear factor-κB, therefore suppressing the effects of TNF-α. In summary, triptolide is able to reverse the TNF-α-associated suppression of osteoblast differentiation, suggesting that triptolide treatment may have a positive effect on bone remodeling and fracture repairing. [ABSTRACT FROM AUTHOR]

ABSTRACT Whereas the vast majority of osteogenesis imperfecta (OI) is caused by autosomal dominant defects in the genes encoding type I procollagen, mutations in a myriad of genes affecting type I procollagen biosynthesis or bone formation and homeostasis have now been associated with rare autosomal recessive OI forms. Recently, homozygous or compound heterozygous mutations in BMP1, encoding the metalloproteases bone morphogenetic protein-1 (BMP1) and its longer isoform mammalian Tolloid (mTLD), were identified in 5 children with a severe autosomal recessive form of OI and in 4 individuals with mild to moderate bone fragility. BMP1/mTLD functions as the procollagen carboxy-(C)-proteinase for types I to III procollagen but was also suggested to participate in amino-(N)-propeptide cleavage of types V and XI procollagens and in proteolytic trimming of other extracellular matrix (ECM) substrates. We report the phenotypic characteristics and natural history of 4 adults with severe, progressive OI characterized by numerous fractures, short stature with rhizomelic shortening, and deformity of the limbs and variable kyphoscoliosis, in whom we identified novel biallelic missense and frameshift mutations in BMP1. We show that BMP1/mTLD-deficiency in humans not only results in delayed cleavage of the type I procollagen C-propeptide but also hampers the processing of the small leucine-rich proteoglycan prodecorin, a regulator of collagen fibrillogenesis. Immunofluorescent staining of types I and V collagen and transmission electron microscopy of the dermis show impaired assembly of heterotypic type I/V collagen fibrils in the ECM. Our study thus highlights the severe and progressive nature of BMP1-associated OI in adults and broadens insights into the functional consequences of BMP1/mTLD-deficiency on ECM organization. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Abstract: Since the resolution of the first three-dimensional structure of a complement component in 1980, considerable efforts have been put into the investigation of this system through structural biology techniques, resulting in about a hundred structures deposited in the Protein Data Bank by the beginning of 2007. By revealing its mechanisms at the atomic level, these approaches significantly improve our understanding of complement, opening the way to the rational design of specific inhibitors. This review is co-authored by some of the researchers currently involved in the structural biology of complement and its purpose is to illustrate, through representative examples, how X-ray crystallography and NMR techniques help us decipher the many sophisticated mechanisms that underlie complement functions. [Copyright &y& Elsevier]

Procollagen C-proteinase (PCP) and its enhancer protein (PCPE) are key to collagen fibril-assembly and extracellular matrix formation. PCP cleaves the carboxyl-propeptides of procollagens types I, II, and III and this initiates the self-assembly of collagen fibrils. PCP can also process pro-lysyl oxidase and laminin 5, and it may cleave the type V procollagen N-propeptides. Procollagen processing by PCP is stimulated by PCPE, a glycoprotein that binds to the C-propeptide of type I procollagen through its N-terminal CUB domains. PCPE is also required for normal cell growth and morphology. Two distinct forms of PCP were isolated from mouse and chick sources. These were recently identified as alternatively spliced products of the gene coding for bone morphogenetic protein-1 (BMP-1), a member of a family of Zn-dependent astacin-like metalloendopeptidases implicated in tissue patterning and development. Typically, these are multidomain proteases that, in addition to their catalytic domain, contain a number of EGF-like and CUB protein-protein interaction domains. Recent evidence suggests that PCP/BMP-1 related proteases can activate TGF- β-like growth factors. There is also evidence for additional alternatively spliced PCP variants. Thus, PCPs may have important biological functions in addition to their role in collagen fibril assembly. [ABSTRACT FROM AUTHOR]

This book chapter describes the use of exogenous application of lysyl oxidase (LOX) and bone morphogenetic protein-1 (BMP1) to enhance collagen synthesis and deposition from fibroblasts in culture. The protocol includes the generation of human embryonic kidney (HEK) 293 cell lines overexpressing human LOX and BMP1 constructs in order to obtain supernatants enriched in these factors. Incubation of fibroblast monolayers with these conditioned media strongly increases the capacity of these cells to deposit collagen onto the insoluble extracellular matrix. We also describe the use of these decellularized fibroblast-derived matrices as a substrate for the growth and differentiation of mesenchymal stem cells., (© 2020 Elsevier Inc. All rights reserved.)

Objectives: To analyze the differential gene and protein expression of Bone Morphogenetic Protein-1 in vaginal tissue of women with advanced pelvic organ prolapse and controls. Study Design: We sampled the anterior vaginal wall of 39 premenopausal (23 patients and 16 controls), and 18 postmenopausal women (13 patients and 5 controls) during hysterectomy. Total mRNAs and proteins were quantified by real-time RT-PCR and immunoblotting. Results: Bone Morphogenetic Protein-1 gene expression was decreased in pre- and postmenopausal pelvic organ prolapse patients compared with asymptomatic women (P = .01). The expression of 130 kDa, 92.5 kDa, and 82.5 kDa isoforms of Bone Morphogenetic Protein-1 were down-regulated in postmenopausal patients (P = .01), whereas the 130 kDa isoform expression was up-regulated in premenopausal patients (P = .009), when compared with respective controls. Conclusion: The Bone Morphogenetic Protein-1 expression in human vagina was altered in patients with severe pelvic organ prolapse and influenced by menopausal status. Dysregulation of Bone Morphogenetic Protein-1 may contribute for a deficient vaginal connective tissue and support. [Copyright &y& Elsevier]