Morphological Changes of Lumbar Vertebral Bodies and Intervertebral Discs Associated With Decrease in Bone Mineral Density of the Spine

Computer aided image analysis was applied to elaborate an automatic method of histomorphometric analysis of trabecular bone samples. Transverse sections of decalcified vertebral bodies were examined using optical microscopy and digital image acquisition system. Further analysis was done by means of a general purpose image analysis package. The same algorithm was applied to all the images tested, thus enabling obtainment of objective and repeatable results. High efficiency in measurements and evaluation of parameters not accessible for manual methods makes this method an interesting alternative for classical histomorphometric analysis. The results obtained demonstrated that assessment of bone mineral density is not sufficient for evaluation of compression strength of vertebral bodies. In contrast, mechanical properties correlate well with histomorphometric parameters. As a consequence it was postulated that compression strength of vertebral bodies is controlled by trabecular structure rather than bone mineral density.

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Abnormal craniofacial and spinal bone development with col2a1a depletion in a zebrafish model of CHARGE syndrome

10.1101/2020.07.10.197533 ◽

2020 ◽

Author(s):

Maximilian Breuer ◽

Maximilian Rummler ◽

Charlotte Zaouter ◽

Bettina M. Willie ◽

Shunmoogum A. Patten

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Bone Development ◽

Morphological Changes ◽

Charge Syndrome ◽

Mineral Density ◽

Zebrafish Model ◽

Weberian Apparatus ◽

Underlying Mechanisms ◽

Osteoblast Markers

AbstractCHARGE syndrome patients commonly display craniofacial abnormalities. Furthermore, most patients show features of idiopathic scoliosis, reduced bone mineral density and in a few cases osteopenia. While several clinical cases and studies have documented the skeletal deformities in CHARGE syndrome bearing CHD7 mutations, the underlying mechanisms of the disorder remain elusive. Here, we detect and quantitatively analyze skeletal abnormalities in larval and adult chd7-/- zebrafish.We show that young chd7-/- larvae present with abnormal craniofacial development, especially related to cartilage. We also observe scoliosis-like spinal deformations at 9 dpf. Gene expression analysis confirmed the reduction of osteoblast markers and Pparγ targets. MicroCT analyses identified abnormal craniofacial structures, Weberian apparatus and vertebral body morphology in chd7-/- mutants, with highly mineralized inclusions, along with significant variances in bone mineral density and bone volume. Notably, we detect a specific depletion of Col2a1a in the cartilage of craniofacial regions and vertebrae, in line with a significantly reduced number of chondrocytes.Our study is the first to elucidate the mechanisms underlying morphological changes in craniofacial structure and vertebrae of adult chd7-/- zebrafish. The chd7-/- mutant zebrafish will be beneficial in future investigations of the underlying pathways of both craniofacial and spinal deformities commonly seen in CHARGE syndrome.

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