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.

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

2001 ◽  
Vol 95 (2) ◽  
pp. 298-307 ◽  
Author(s):  
Gregory A. Helm ◽  
Jin Zhong Li ◽  
Tord D. Alden ◽  
Sarah B. Hudson ◽  
Elisa J. Beres ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Skeletal Development ◽  
Light And Electron Microscopy ◽  
Mesenchymal Cell ◽  
Ultrastructural Changes ◽  
Endochondral Bone Formation ◽  
Electron Microscopic ◽  
Content Type ◽  
Time Points ◽  
Fine Print

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 have attracted the greatest interest. Expression of the BMP-13 gene is 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/neoligament 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 units of adenovirus (Ad)-BMP-13 or Ad-β-galactosidase in the thigh musculature, and the region was examined using light and electron microscopy at various time points between 2 days 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 treated tissue displayed the histological and ultrastructural appearance of neotendon/neoligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the treated tissue. A short-term bromodeoxyuridine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection. At all time points, the control AD-β-gal injection sites were found to contain only normal muscle, without evidence of inflammation or mesenchymal cell proliferation. Conclusions. The results of this study indicate 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 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.

scholarly journals Role of Interleukin-10 in Endochondral Bone Formation in Mice: Anabolic Effect via the Bone Morphogenetic Protein/Smad Pathway

2013 ◽  
Vol 65 (12) ◽  
pp. 3153-3164 ◽  
Author(s):  
Youn-Kwan Jung ◽  
Gun-Woo Kim ◽  
Hye-Ri Park ◽  
Eun-Ju Lee ◽  
Je-Yong Choi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Interleukin 10 ◽  
Endochondral Bone Formation ◽  
Anabolic Effect ◽  
Endochondral Bone ◽  
Smad Pathway ◽  
Morphogenetic Protein

Identifying Candidate Mechanoregulators of Skeletal Development

2009 ◽  
Author(s):  
Niamh C. Nowlan ◽  
Patrick J. Prendergast ◽  
Shahragim Tajbakhsh ◽  
Paula Murphy
Keyword(s):  
Skeletal Muscle ◽  
Endochondral Ossification ◽  
Muscle Development ◽  
Skeletal Development ◽  
Endochondral Bone Formation ◽  
Mechanical Forces ◽  
Endochondral Bone ◽  
Mutant Strains ◽  
The Relationship

Studying the relationship between mechanical forces and skeletal development can provide vital clues to the mechanoregulation of skeletogenesis, providing important information to tissue engineers hoping to create functional cartilage or bone in vitro. Many studies of the mechanoregulation of skeletal development have focused on the chick embryo e.g., [1, 2]. However, as no endochondral ossification takes place in the embryonic chick long bones [1], mammalian systems must be used to examine the effect of mechanical forces on endochondral bone formation. Mouse mutant strains exist in which muscle development is affected, providing models with which to examine skeletogenesis in the absence of skeletal muscle contractions. One such strain is Pax3sp/sp [3], also known as splotch. The splotch mutant lacks the transcription factor Pax3, which prevents the migration of muscle pre-cursor cells into the limb buds, resulting in a complete absence of skeletal muscle.

Ultrastructural Changes of the Olfactory Epithelium in Alzheimer's Disease

1992 ◽  
Vol 6 (6) ◽  
pp. 219-225 ◽  
Author(s):  
Bruce W. Jafek ◽  
Pamela M. Eller ◽  
Edward W. Johnson ◽  
Mary M. Chapman ◽  
Christopher M. Filley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Olfactory Epithelium ◽  
Ultrastructural Changes ◽  
Electron Microscopic Level ◽  
Histopathological Changes ◽  
Electron Microscopic ◽  
Normal Tissues ◽  
Olfactory Receptor Cells ◽  
Ultrastructural Appearance

Recent studies have demonstrated an association between abnormalities in the sense of smell and Alzheimer's disease (AD). In our laboratory we have shown that olfactory dysfunction is accompanied by histopathological changes in the olfactory epithelium. These findings led us to believe that there were changes in the olfactory epithelium in AD that resulted in altered olfactory function. In the present study we have done biopsies of tissue from 12 patients who have been screened thoroughly and diagnosed with probable AD. Olfactory epithelium from 10 of these patients has been examined at the electron microscopic level. The overall appearance of the epithelium is altered from that seen in normosmic, age-matched controls. The ultrastructural appearance of olfactory receptor cells and support cells is disrupted. In addition, a crystallinelike material has been observed over the surface of the olfactory epithelium in six patients. This material was not observed in the respiratory epithelium of the same patients and has not been seen by us in any other pathological or normal tissues we have examined. The overall appearance of the olfactory epithelium in these probable AD patients seems to be unique when compared with other pathological states examined so far. The present study suggests that olfactory epithelium biopsy may be useful in the early detection of AD.

scholarly journals Heterotopic ossification in a patient with diffuse idiopathic skeletal hyperostosis: Input from histological findings

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Caterina Licini ◽  
Luca Farinelli ◽  
Giorgia Cerqueni ◽  
Andrell Hosein ◽  
Saverio Marchi ◽  
...  
Keyword(s):  
Heterotopic Ossification ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Bone Morphogenetic Protein 2 ◽  
Endochondral Bone Formation ◽  
Surgical Trauma ◽  
Endochondral Bone ◽  
Morphogenetic Protein ◽  
High Incidence

A high incidence of heterotopic ossification (HO) has been reported in patients with diffuse idiopathic skeletal hyperostosis (DISH), a metabolic disease characterized by calcifications of entheses at spine and peripheral sites. We performed histological and immunohistochemical analyses in five different HO sites in a patient with DISH to study a possible mutual interaction of bone morphogenetic protein 2 (BMP-2), transforming growth factor beta (TGF-β), and decorin, crucial for bone mass increasing, matrix calcification, and endochondral bone formation. We speculated that the surgical trauma triggered HO, inducing TGF-β release at the lesion site. TGF-β recruits osteoblast precursor cells and determines the overexpression of BMP-2 in the surrounding skeletal muscle, inducing a further osteogenic differentiation, contributing to HO onset.

Chondrogenesis of a non-collagen-based cartilage in the sea lamprey, Petromyzon marinus

1996 ◽  
Vol 74 (12) ◽  
pp. 2118-2130 ◽  
Author(s):  
Kim M. McBurney ◽  
Glenda M. Wright
Keyword(s):  
Petromyzon Marinus ◽  
Light And Electron Microscopy ◽  
Mesenchymal Cell ◽  
Sea Lamprey ◽  
Structural Protein ◽  
Cartilage Differentiation ◽  
Ultrastructural Appearance ◽  
Parallel Arrays ◽  
Two Peaks ◽  
The Brain

Chondrogenesis of the trabeculae, non-collagen-based cartilages in prolarval stages of the sea lamprey, Petromyzon marinus, was examined by light and electron microscopy. Chondrogenesis of the trabecular cartilages in prolarval lampreys commenced with the formation of mesenchymal condensations. Two peaks in mesenchymal cell density occurred, one prior to condensation formation and a second immediately before cartilage differentiation. The possibility of inductive influences by epithelio-mesenchymal interactions on the initiation of chondrogenesis is discussed. Bilateral condensations first appeared by day 17 post fertilization ventromedial to the eyes in a band of tightly packed yolk-laden mesenchymal cells that represent neural crest derived tissue. Cartilage differentiation occurred by day 19 post fertilization and was indicated by the presence of matrix-synthesizing organelles and the first ultrastructural appearance in the extracellular matrix of lamprin, a structural protein unique to lamprey cartilage. Lamprin was initially deposited as discrete 15- to 40-nm globules. Subsequently, lamprin appeared as fibrils aggregated into branching and parallel arrays arranged in pericellular, territorial, and interterritorial zones. Lengthening of the trabecular cartilages was primarily by appositional growth at the rostral end. The timing of the appearance of trabecular cartilages in prolarval stages likely reflects the functional importance of these structures for supporting the brain as the lamprey initiates burrowing behaviour.

A comparative study on the gastroduodenal tolerance of different antianaemic preparations

2003 ◽  
Vol 22 (3) ◽  
pp. 137-141 ◽  
Author(s):  
M A Idoate Gastearena ◽  
A G Gil ◽  
A Azqueta ◽  
M P Coronel ◽  
M Gimeno
Keyword(s):  
Protective Effect ◽  
Ferrous Sulphate ◽  
Light And Electron Microscopy ◽  
Mucosal Damage ◽  
Duodenal Mucosa ◽  
Ultrastructural Changes ◽  
Electron Microscopic ◽  
Ultrastructural Alteration ◽  
Iron Protein ◽  
Microscopic Studies

The most significant adverse effect of repeated oral administration of iron-containing antianaemic preparations is the gastroduodenal toxicity, attributable to a direct toxic effect of iron on the glandular epithelium. To assess gastroduodenal mucosal damage and the potential protective effect of different antianaemic preparations, a study was carried out to compare the gastroduodenal toxicity caused by three different types of antianaemic drugs in normal and anaemic rats administered at repeated therapeutic doses. Histological damage to the gastroduodenal mucosa was evaluated using light and electron microscopy. In both normal and anaemic rats, pathological changes were less marked in animals treated with ferrimannitol-ovoalbumin (TM/ FMOA) than in those treated with iron protein succinylate or ferrous sulphate. Electron microscopic studies of duodenal mucosa in normal rats treated with iron protein succinylate and ferrous sulphate confirmed a severe ultrastructural alteration, whereas no changes were detected in animals treated with TM/FMOA. In anaemic rats, slight duodenal ultrastructural changes were noted with all three types of treatment. The effectiveness of the preparations in resolving the anaemia was similar in the three groups. It was concluded that TM/FMOA exerts a protective effect against the toxicity normally observed of the iron in other formulations in normal and anaemic rats, which was attributed to the fact that administration of iron bound to a protein core allows for gradual release of iron.

Sign in / Sign up

Export Citation Format

Share Document