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Updated: Dec 25, 2025

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
Published on: July 8, 2021
Temporal and spatial expression of Sox9, Pax1, TGF-β1 and type I and II collagen in human intervertebral disc
1Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopaedic Diseases Liaoning Province, Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, 116011 Dalian, People's Republic of China.
Purpose:
An accurate understanding of cellular biochemical changes in human intervertebral disc (IVD)s and the corresponding mechanisms during the developmental process still remain unknown and important for investigating the function of critical factors in normal IVD development as well as ascertaining the therapeutic targets for the IVD degeneration.
Methods:
Under ethical conditions, human fetal cervical IVDs at 4, 5, and 6 months of pregnancy were collected at abortion surgery. Normal adult human C3-C7 cervical IVDs were taken from cadaveric donors. Sox9, Pax1, TGF-β1 and type I/II collagen protein and RNA were detected. The number of positive cells was counted to calculate the optical density value for each factor.
Results:
Sox9, Pax1, and TGF-β1 expression in the IVD was remarkably reduced with the developmental stage. The location of high expression of Sox9, Pax1, and TGF-β1 changed with the developmental stage, and migrated from the nucleus pulposus to the annulus fibrosus and endplate. Higher Sox9, Pax1, and TGF-β1 expression was finally observed around the sclerotome of the vertebral body. The anabolism of type I/II collagens is significantly increased in the IVD in the mid-trimester fetus.
Conclusions:
Sox9, Pax1 and TGF-β1 participate in the developmental process of the human IVD and vertebral body. However, these factors show a separate expression of mRNA and protein, suggesting that they are expressed in the strict time and spatial order.
Insights
Sox9, Pax1, and TGF-β1 expression decreases during human intervertebral disc (IVD) development, migrating to the vertebral body. Collagen anabolism increases, highlighting key factors in IVD development and degeneration.
Area of Science:
- Developmental Biology
- Biochemistry
- Regenerative Medicine
Background:
- Understanding human intervertebral disc (IVD) development is crucial for identifying therapeutic targets for IVD degeneration.
- Cellular biochemical changes and underlying mechanisms during IVD development are not fully understood.
Purpose of the Study:
- To investigate the expression patterns of key developmental factors (Sox9, Pax1, TGF-β1) and collagen anabolism during human IVD development.
- To elucidate the roles of these factors in normal IVD development and their potential relevance to IVD degeneration.
Main Methods:
- Collection of human fetal cervical IVDs (4-6 months gestation) and adult cervical IVDs from cadavers.
- Detection of Sox9, Pax1, TGF-β1 protein and RNA using immunohistochemistry and RT-PCR.
- Quantification of positive cells and optical density to assess factor expression levels.
Main Results:
- Sox9, Pax1, and TGF-β1 expression significantly decreased with advancing developmental stage in human IVDs.
- Expression localization of Sox9, Pax1, and TGF-β1 shifted from the nucleus pulposus to the annulus fibrosus and endplate, eventually localizing near the vertebral body sclerotome.
- Anabolism of type I and type II collagens was notably elevated in mid-trimester fetal IVDs.
Conclusions:
- Sox9, Pax1, and TGF-β1 are integral to human IVD and vertebral body development.
- Differential mRNA and protein expression of these factors indicates strict temporal and spatial regulation during development.
- These findings provide insights into normal IVD development and potential targets for treating IVD degeneration.
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