scholarly journals Bone morphogenetic protein in spinal fusion: overview and clinical update

2001 ◽  
Vol 10 (4) ◽  
pp. 1-6 ◽  
Author(s):  
Brian R. Subach ◽  
Regis W. Haid ◽  
Gerald E. Rodts ◽  
Michael G. Kaiser
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Morphogenetic Protein ◽  
Differentiation Factors ◽  
Efficiency Cost ◽  
Spinal Arthrodesis

The widespread use of fusion procedures in the management of spinal disorders has led investigators to explore the use of growth and differentiation factors in such procedures. As an adjuvant to allograft bone or as a replacement for harvested autograft, bone morphogenetic proteins (BMPs) appear to improve fusion rates after spinal arthrodesis in both animal models and humans, while reducing the donor-site morbidity previously associated with such procedures. The use of recombinant genetic technology in the production of BMP has improved the efficiency, cost effectiveness, and safety of producing and using such materials. Recombinant human BMP-2 (rhBMP-2), as one of the first factors identified in the process of endochondral bone formation, has been extensively researched over the past decade. The efficacy and dose profile of this differentiation factor in the context of various carrier substrates has been investigated. Based on the encouraging results of preliminary studies, the future role of rhBMP-2 may lie in its replacement of autologous bone grafting and, consequently, the reduced need for instrumented fixation, while concurrently improving overall fusion rates. The authors provide an overview of BMP and review its use in clinical and laboratory settings.

A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein–13 adenoviral gene therapy

2000 ◽  
Vol 8 (4) ◽  
pp. 1-8 ◽  
Author(s):  
Gregory A. Helm ◽  
Jin Zhong Li ◽  
Tord D. Alden ◽  
Sarah A. Hudson ◽  
Elisa J. Beres ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Skeletal Development ◽  
Light And Electron Microscopy ◽  
Mesenchymal Cell ◽  
Ultrastructural Changes ◽  
Endochondral Bone Formation ◽  
Electron Microscopic ◽  
Endochondral Bone ◽  
Morphogenetic Protein ◽  
Ultrastructural Appearance

Object Bone morphogenetic proteins (BMPs) are involved in the growth and development of many tissues, but it is their role in skeletal development and their unique ability to induce ectopic and orthotopic osteogenesis that has attracted the greatest interest. Expression of the BMP-13 gene has been shown to be predominantly localized to hypertrophic chondrocytes in regions of endochondral bone formation during development, as well as in mature articular cartilage in the adult. In addition, the application of BMP-13 on a collagen carrier induces neotendon/ligament formation when delivered subcutaneously or intramuscularly in rodents. The aim of the present study was to determine the histological and ultrastructural changes that occur after the intramuscular injection of a first-generation BMP-13 adenoviral vector. Methods Athymic nude rats were injected with 3.75 × 1010 plaque-forming unit adenovirus (Ad)-BMP-13 or Ad-β-galactosidase in the thigh musculature, and the regions examined using light and electron microscopy at various time points between 2 and 100 days postinjection. As early as 2 days after injection of Ad-BMP-13, progenitor cells were observed infiltrating between the transduced muscle fibers. These cells subsequently proliferated, differentiated, and secreted large amounts of collagenous extracellular matrix. By 100 days postinjection, the induced tissue had the histological and ultrastructural appearance of neotendon/ligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the induced tissue. A short-term bromodeoxyuri-dine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection. Conclusions The results of this study suggest that in the future the use of the BMP-13 gene may have therapeutic utility for the healing of tendon and ligament tears and avulsion injuries.

scholarly journals The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression

2020 ◽  
Vol 21 (7) ◽  
pp. 2358 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Adult Population ◽  
Cartilage Damage ◽  
Natural Process ◽  
Joint Disease ◽  
Endochondral Bone Formation ◽  
Potential Therapeutic Target ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Age Related

Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management.

Key role of the expression of bone morphogenetic proteins in increasing the osteogenic activity of osteoblast-like cells exposed to shock waves and seeded on bioactive glass-ceramic scaffolds for bone tissue engineering

2014 ◽  
Vol 29 (5) ◽  
pp. 728-736 ◽  
Author(s):  
Giuliana Muzio ◽  
Germana Martinasso ◽  
Francesco Baino ◽  
Roberto Frairia ◽  
Chiara Vitale-Brovarone ◽  
...  
Keyword(s):  
Shock Wave ◽  
Alkaline Phosphatase ◽  
Shock Waves ◽  
Bioactive Glass ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Glass Ceramic ◽  
Osteogenic Activity ◽  
Morphogenetic Protein

In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine.

scholarly journals Bone Morphogenetic Proteins in Craniofacial Surgery: Current Techniques, Clinical Experiences, and the Future of Personalized Stem Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Kristofer E. Chenard ◽  
Chad M. Teven ◽  
Tong-Chuan He ◽  
Russell R. Reid
Keyword(s):  
Stem Cell ◽  
Bone Morphogenetic Proteins ◽  
Bone Grafting ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
Experimental Models ◽  
Craniofacial Surgery ◽  
Cell Therapies ◽  
Autologous Bone Grafting ◽  
Autologous Bone

Critical-size osseous defects cannot heal without surgical intervention and can pose a significant challenge to craniofacial reconstruction. Autologous bone grafting is the gold standard for repair but is limited by a donor site morbidity and a potentially inadequate supply of autologous bone. Alternatives to autologous bone grafting include the use of alloplastic and allogenic materials, mesenchymal stem cells, and bone morphogenetic proteins. Bone morphogenetic proteins (BMPs) are essential mediators of bone formation involved in the regulation of differentiation of osteoprogenitor cells into osteoblasts. Here we focus on the use of BMPs in experimental models of craniofacial surgery and clinical applications of BMPs in the reconstruction of the cranial vault, palate, and mandible and suggest a model for the use of BMPs in personalized stem cell therapies.

The role of Akt1 in terminal stages of endochondral bone formation: Angiogenesis and ossification

Bone ◽  
2009 ◽  
Vol 45 (6) ◽  
pp. 1133-1145 ◽  
Author(s):  
Veronica Ulici ◽  
Katie D. Hoenselaar ◽  
Hanga Agoston ◽  
David D. McErlain ◽  
Joseph Umoh ◽  
...  
Keyword(s):  
Bone Formation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

scholarly journals Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing

2020 ◽  
Vol 21 (7) ◽  
pp. 2365 ◽  
Author(s):  
Tsuyoshi Shimo ◽  
Hiroaki Takebe ◽  
Tatsuo Okui ◽  
Yuki Kunisada ◽  
Soichiro Ibaragi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Fracture Healing ◽  
P38 Mapk ◽  
Inverse Agonist ◽  
Endochondral Bone Formation ◽  
Dependent Manner ◽  
Retinoid Receptor ◽  
Endochondral Bone ◽  
Inverse Agonists

The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.

BMP AS AN ALTERNATIVE TO AUTOGRAFT FOR SPINAL ARTHRODESIS

2002 ◽  
Vol 06 (01) ◽  
pp. 31-42
Author(s):  
Michael N. Magin ◽  
Lex R. Giltaij
Keyword(s):  
Large Scale ◽  
Donor Site ◽  
Biomechanical Testing ◽  
Primary Stability ◽  
Donor Site Morbidity ◽  
Histological Evaluation ◽  
Osteogenic Potential ◽  
Iliac Crest Bone Graft ◽  
Spinal Arthrodesis ◽  
Potent Growth

The gold standard in spinal arthrodesis is still given by the use of autograft. Additional operations to obtain bone grafts increase morbidity and strain for the patient, but do not always provide bone with sufficient primary stability and high osteogenic potential. Despite the use of large-scale conventional techniques, applying posterior and anterior access, failures still occur and lead to loss of correction or, even worse, to persistent instability. Therefore, a study has been designed to determine whether spinal arthrodesis could improved by the use of BMP-7, a potent growth factor with osteogenic properties, in comparison with autograft. Following disc removal and monosegmental instrumentation of the sheep lumbar spine, we compared interbody fusion at six months after administration of autogenous iliac crest bone graft, and BMP-7 (rhOP-1). Spinal arthrodesis quality was examined by plain X-ray, computed tomography (CT scan), biomechanical testing and histological evaluation. All examination methods demonstrated superior fusion after administration of BMP. Autograft eventually produced bony healing in most cases, however of a lower quality than with BMP. The results indicate that the use of BMP is enhancing vertebral arthrodesis in sheep. As well as offering the potential for improved bone healing, the use of BMP may permit less invasive surgery, such as vertebroplasty, kyphoplasty or application of cages, and help to avoid donor site morbidity.

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