2. Academic Validation
  3. Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model

Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model

  • Int J Mol Sci. 2019 Oct 20;20(20):5198. doi: 10.3390/ijms20205198.
Holly Dupuis 1 2,  Michael Andrew Pest 3 4,  Ermina Hadzic 5 6,  Thin Xuan Vo 7,  Daniel B Hardy 8 9,  Frank Beier 10 11
Affiliations

Affiliations

  • 1 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. hkipp@uwo.ca.
  • 2 Western Bone and Joint Institute, Western University London, London, ON N6A 5C1, Canada. hkipp@uwo.ca.
  • 3 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. mpest@uwo.ca.
  • 4 Western Bone and Joint Institute, Western University London, London, ON N6A 5C1, Canada. mpest@uwo.ca.
  • 5 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. ehadzic2@uwo.ca.
  • 6 Western Bone and Joint Institute, Western University London, London, ON N6A 5C1, Canada. ehadzic2@uwo.ca.
  • 7 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. Thinxv@gmail.com.
  • 8 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. Daniel.Hardy@schulich.uwo.ca.
  • 9 Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. Daniel.Hardy@schulich.uwo.ca.
  • 10 Departments of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University London, London, ON N6A 5C1, Canada. fbeier@uwo.ca.
  • 11 Western Bone and Joint Institute, Western University London, London, ON N6A 5C1, Canada. fbeier@uwo.ca.
PMID: 31635173 DOI: 10.3390/ijms20205198
Abstract

Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. RXR agonist-treated rats had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence with p57 immunostaining. Additionally, SOX9-positive cells were found surrounding the calcified tissue. The epiphysis of SR11237-treated bones showed increased TRAP staining and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of the treated Animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models.

Keywords

chondrocytes; endochondral ossification; osteoarthritis; retinoid X receptor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-107413
    99.91%, RXR-Selective Agonist
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