Developmental and Acquired Disorders of The Spine
Milosh Perovitch in Radiological Evaluation of the Spinal Cord, 2019
Achondroplasia is a disorder that differs from those described above. It is characterized by the defect of endochondral ossification that leads to dwarfism. This inborn error in the development of cartilage is associated with retarded growth of the skeletal system. The disturbances in the growth include the longitudinal development of the bony spine which is equally delayed. The progress of different bony components of the spine, such as vertebral bodies, laminae, neural arches, and pedicles, is impeded, and they remain short and considerably thicker because of an increased periosteal bone formation. This thickening represents the cause of a considerable narrowing of the spinal canal, usually accompanied by a severe thoracolumbar kyphosis. A subluxation of one or more vertebrae can further on contribute to the spinal cord compression, and thereby accelerate the development of neurological symptoms and complications. Owing to the compression of the spinal cord and cauda equina by these structural changes, a slowly progressive neurological syndrome will become apparent. Neurological symptoms may occur abruptly if a minor protrusion of a disk imposes further reduction of an already stenotic spinal canal, and even a complete block of the subarachnoid space is possible. Occasionally, the whole length of the lumbar and distal thoracic canal is obstructed at each intervertebral level. In patients with achondroplasia in whom a myelography had to be performed, we used oxygen as a contrast medium because of considerable difficulties in forcing the opaque insoluble contrast to move cranially in the stenotic canal.
Nutritional Regulation of the Growth Plate
Crystal D. Karakochuk, Kyly C. Whitfield, Tim J. Green, Klaus Kraemer in The Biology of the First 1,000 Days, 2017
During embryonic development, bone formation begins with the condensation of mesenchymal stem cells. In a number of places in the body, such as the flat bones of the skull, bone formation is driven by a process called intramembranous ossification, where mesenchymal stem cells differentiate directly into bone-forming osteoblasts. In most other places, however, bones are formed by a different process known as endochondral ossification (Figure 16.1; for review, see Kronenberg [1]). In this process, mesenchymal stem cells first differentiate into chondrocytes. These chondrocytes secrete cartilage matrix composed mainly of type II collagen. Proliferation of chondrocytes leads to an overall expansion of this cartilage tissue and, in the center of the cartilage, cells stop dividing and start enlarging to become type X collagen-producing hypertrophic chondrocytes. These hypertrophic chondrocytes drive cartilage matrix mineralization, and eventually undergo apoptosis, leaving a cartilage matrix scaffold for the invasion of blood vessels and osteoblasts to lay down bone matrix in the center of the cartilage, known as the primary ossification center. As chondrocytes continue to proliferate, undergo hypertrophy, and are then invaded by osteoblasts, the long bones continue to lengthen and ossify in the center, resulting in longitudinal bone growth and an overall increase in body size and height. Gradually, as bones continue to grow in length, endochondral ossification becomes increasingly restricted to the cartilaginous structure found near the two opposite ends of long bones known as the growth plate. Within each growth plate, chondrocytes are arranged into three histologically distinct zones called resting, proliferative, and hypertrophic zones. Closest to the epiphysis, round and slowly dividing resting chondrocytes serve as precursor cells capable of self-renewing and giving rise to new clones of proliferative chondrocytes. In the proliferative zones, cells are arranged in columns parallel to the long axis of the bone and, within each column, chondrocytes undergo rapid proliferation, pushing themselves gradually toward the center of the bone, where they undergo the same process of hypertrophy and apoptosis. In late adolescence, as adult height is gradually attained, the growth plate continues to narrow, until growth potential is depleted, the epiphyseal fuses, and growth in height stops.
Next Generation Tissue Engineering Strategies by Combination of Organoid Formation and 3D Bioprinting
Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon in Tissue Engineering Strategies for Organ Regeneration, 2020
The main challenge of tissue engineers is to fabricate clinically relevant patient-specific constructs. Recently, conventional tissue engineering is experiencing a paradigm shift toward “developmental engineering” (Lenas et al. 2009). Now, tissue regeneration strategies are directed towards understanding how precisely in vitro tissue engineering strategies can mimic in vivo developmental processes (Rivron et al. 2009). Some of the initial steps in this direction include the study by Scotti et al. which utilized the capacity of human MSC to generate bone tissue simulating in vivo like endochondral program to develop a model to study mechanisms of bone development using transwell culture (Scotti et al. 2010). The idea behind their approach was to replicate the process of bone development (endochondral ossification, a process via which most of the long bones of the limbs, vertebrae and rib-cage develop in vivo). The key event in the process of endochondral ossification is the development of cartilaginous template that later develops into bone as opposed to intramembranous ossification that is involved with craniofacial bone development that occurs without any intermediate cartilaginous template. Till now, the bone tissue engineering strategies mostly used direct differentiation protocols. Such bone models generated via a “developmental engineering” paradigm could generate advanced grafts for bone regeneration following architecture of woven bone or cancellous bone, if combined with bioprinting strategies (Scotti et al. 2010). However, this study was based on spheroids and transwell based approaches and thus could not replicate the anatomical architecture and thickness of native bone tissue. Thus, to further extend this understanding, recently, in our laboratory we utilized such a strategy where similar endochondral ossification inspired protocol was utilized and combined with 3D bioprinting to develop bone tissue equivalents. Simulation of the developmental-biology-inspired endochondral ossification route in the MSC laden silk-gelatin 3D bioprinted constructs triggered the Wnt/β-catenin, IHH and parathyroid hormone (PTH), signaling in vitro osteogenic differentiation, leading to improved osteogenic differentiation potential of MSCs and augmented mineral deposition (Chawla et al. 2018). Another significant event during embryogenesis is gastrulation that involves patterning of pluripotent epiblast into the three germ layers that later develops into the embryo. This event involves a signaling pathway involving the BMP, Wnt and Nodal pathways (Chhabra et al. 2018). Thus, replication of such events seems quintessential to the approach of developmental biology inspired tissue engineering strategies (Fig. 4.2). This section would be incomplete without the mention of another interesting phenomenon of developmental biology, that is, directed tissue assembly, a process where closely placed tissue spheroids undergo fusion to replicate this fundamental biophysical and biological principle of directed tissue assembly (Mironov et al. 2009). Tissue engineers tried to take cues from this process and incorporated those features with 3D bioprinting, that led to the emergence of the new field of organ printing that holds promise to design and fabricate engineered tissue/mini organs for repair, regeneration and replacement of injured or damaged organs.
Visualization of Different Tissues Involved in Endochondral Ossification With Alcian Blue Hematoxylin and Orange G/Eosin Counterstain
Published in Journal of Histotechnology, 2008
Jessica R. Nowalk, Lisa M. Flick
The histologic evaluation of endochondral ossification is critical to the study of fracture healing, developmental biology, and comparative histology. A modification of Sayers' alcian blue hematoxylin staining technique is described in which a different counterstain is applied. Paraffin sections are stained in alcian blue hematoxylin for 30 min, and then placed in orange G-eosin counterstain for 1 min, 30 s. This method can differentiate cartilage, mature bone, and immature bone found in various stages of endochondral ossification and fracture callus. Increasing the hematoxylin content to 0.5% produced a more striking contrast between the bone and cartilaginous aspects of the healing fracture callus. Inclusion of orange G (instead of acid fuchsin) in the counterstain provides better demarcation of mature and immature bone. Alcian blue hematoxylin/orange G-eosin consistently stains cartilage blue, mature bone orange, and immature bone mauve and is particularly suited to the study of endochondral ossification, fracture healing, and bone remodeling. (The J Histotechnol 31:19, 2008) Submitted May 29, 2007; accepted with revisions October 1, 2007
Histone deacetylase 3 suppresses Erk phosphorylation and matrix metalloproteinase (Mmp)-13 activity in chondrocytes
Published in Connective Tissue Research, 2017
Lomeli R. Carpio, Elizabeth W. Bradley, Jennifer J. Westendorf
Histone deacetylase (Hdac3) inhibitors are emerging therapies for many diseases including cancers and neurological disorders; however, these drugs are teratogens to the developing skeleton. Hdac3 is essential for proper endochondral ossification as its deletion in chondrocytes increases cytokine signaling and the expression of matrix remodeling enzymes. Here we explored the mechanism by which Hdac3 controls matrix metalloproteinase (Mmp)-13 expression in chondrocytes. In Hdac3-depleted chondrocytes, extracellular signal-regulated kinase (Erk)1/2 as well as its downstream substrate, Runx2, were hyperphosphorylated as a result of decreased expression and activity of the Erk1/2 specific phosphatase, Dusp6. Erk1/2 kinase inhibitors and Dusp6 adenoviruses reduced Mmp13 expression and partially rescued matrix production in Hdac3-deficient chondrocytes. Postnatal chondrocyte-specific deletion of Hdac3 with an inducible Col2a1-Cre caused premature production of pErk1/2 and Mmp13 in the growth plate. Thus, Hdac3 controls the temporal and spatial expression of tissue-remodeling genes in chondrocytes to ensure proper endochondral ossification during development.
Histochemical Analysis of Enzymes Involved in the Formation and Metabolism of the Nasal Septal Cartilage
Published in Acta Oto-Laryngologica, 1992
Formation of the nasal septal cartilage in prenatal and neonatal rats was studied histologically and by histochemistry to determine the manner, degree and participation of the nasal septal cartilage in midface growth and in bone formation of the face. Chondrogenesis of the nasal septal cartilage started at the 13th embryonic day, premaxillary and vomerin bone formation at the 14th embryonic day and endochondral bone formation of the septo-presphenoid area at the 17th embryonic day. After differentiation of the nasal septal cartilage, this cartilage supported ethmoid bone formation by endochondral ossification in the septo-presphenoid area. Nasal septal cartilage showed intense activity of lactate dehydrogenase, NADH2-diaphorase and a moderate activity of acid phosphatase, whereas premaxillary and vomerin bone showed intense activity of akaline phosphatase. Osteoblasts showed intense activity of alkaline phosphatase, lactate dehydrogenase and NADH2-diaphorase and osteoclasts showed intense activity of acid phosphatase. During the embryonal period growth of the nasal septal cartilage could occur in an ethmoido-rostral direction supported by endochondral ossification and growth in length and height supported by apposition and interstitial growth.
Related Knowledge Centers
- Bone Healing
- Fetus
- Hyaline Cartilage
- Intramembranous Ossification
- Skeleton
- Long Bone
- Osseous Tissue