Cartilage Repair Tissue 'Substantially Different'

When a horse sustains a serious injury to articular cartilage in one of its joints, a repair process occurs in the wound. The hope of the horse's owner is for the injury to sufficiently heal and restore normal joint function. Unfortunately, for much of the horse's life, there is a high probability that osteoarthritis will cause chronic pain and compromised joint function.

Through research performed at the Gluck Equine Research Center, Jamie MacLeod, VMD, PhD, and Michael Mienaltowski, DVM, PhD, studied the repair tissue that forms within full-thickness lesions of articular cartilage. This project was conducted in collaboration with equine orthopaedic surgeons David Frisbie, DVM, PhD, and Wayne McIlwraith, BVSc, PhD, FRCVS, DSc, DMV, Dipl. ACVS, at Colorado State University. The research was published in the open access journal BMC Medical Genomics.

Bone and cartilage stain

Figure 1. A sample of tissue containing both normal cartilage and repair tissue was stained with chemicals used to help visualize cellular and tissue structure (H&E stain, top photo). A special stain was also used to detect proteoglycans in the sample; red staining indicated that the articular cartilage surrounding the lesion contains proteoglycans, while blue staining indicates deficiency within the repair tissue.

Researchers compared repair tissue from full-thickness lesions, on which surgeons performed arthroscopic debridement and microfracture treatment (a procedure performed to remove damaged tissue and create small holes into the underlying bone tissue to allow blood and cells access to the lesioned area), to normal articular cartilage of the distal femur (thigh bone) in horse stifles four months after surgery. When they examined the tissue microscopically, they noted the relatively normal cartilage surrounding the lesion looked clearly different from the repair tissue within the injury. Key differences were (see Figure 1):

  • The repair tissue did not restore normal cartilage structure
  • The edges of the repair tissue did not integrate well with the surrounding cartilage
  • By special staining, in most cases, repair tissue seemed to be missing proteoglycan, a key molecular component of normal cartilage that helps provide compressive strength to cartilage
  • The repair tissue did not restore a smooth articular surface

The research team used a powerful new scientific technique called microarray-based transcriptional profiling to compare gene expression of repair tissue and normal cartilage. The technique allowed them to study the expression of thousands of genes simultaneously. By following which groups of genes were active in each of the tissues, they were able to determine that the tissues have substantial functional dissimilarities. For example, transcript levels for all conventional biomarkers typically used to describe healthy articular cartilage were found at higher levels in normal cartilage relative to the repair tissue. In addition, the expression of many genes typically associated with scar tissue or fibrocartilage, which is much more rigid and less amenable to withstanding the forces encountered in a horse's joint, was detected at greater levels in repair tissue. Thus, the researchers saw that differences in expression patterns of many functionally important groups of genes were associated with repair tissue, providing new insight into why the healing process of full-thickness articular lesions is inadequate.

In this study the research team concluded that repair tissue occupying full-thickness articular lesions is functionally very different from normal articular cartilage. The cells within repair tissue do not achieve a normal pattern of gene expression necessary to restore and maintain healthy articular cartilage structure and function. Future research should focus on how to direct the cells in repair tissue to function more like cells in articular cartilage. New treatment options could allow for better, more cartilagelike healing, which restores the structural and biomechanical integrity of the joint surface.

Michael Mienaltowski, DVM, PhD, a postdoctoral research fellow at the University of South Florida, Department of Orthopaedics & Sports Medicine and Department of Pathology & Cell Biology, completed his PhD research at the Gluck Equine Research Center, supported in part by a grant from the Morris Animal Foundation.

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More information on Gluck Equine Research Center, and UK's Equine Initiative.  

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