Localization and Function of Sulfated Proteoglycans in the Equine Digital Laminae

Article Outline

• Take Home Message
• Introduction
• Materials and Methods
• Results
• Discussion
• Clinical Relevance
• Conclusion
• Copyright

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Take Home Message 

Polysulfated proteoglycans of the lamellar extracellular matrix (ECM) are similar to those of articular cartilage and hence may maintain hydration and resistance to compression.

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Introduction 

We have previously shown that ADAMTS-4 (aggrecanase), which is implicated in the pathophysiology of osteoarthritis through cleavage of large polysulfated proteoglycans, is elevated in experimentally induced and naturally acquired equine laminitis. To understand the role played by ADAMTS-4 in equine laminitis, it is necessary to localize substrates within the digital lamellae and to determine their contribution to lamellar structure and function.

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Materials and Methods 

Aggrecan, chondroitin-6-sulfate, keratan sulfate, laminin, and hyaluran were detected via immunofluorescence in 10μm sections of lamellae. Specificity of antibodies was confirmed by Western blotting and by peptide competition.

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Results 

Aggrecan and hyaluran appear to be largely concentrated in the secondary epidermal lamellae, while keratan sulfate and chondroitin sulfate display varying and unique distributions throughout the tissue.

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Discussion 

Proteoglycan components of the lamellar ECM are similar to those of articular cartilage, consistent with the possibility that they protect the lamellae against general and localized compression resulting from weight bearing and motion-associated rotation of the third phalanx.

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Clinical Relevance 

We propose that degradation of lamellar ECM large polysulfated proteoglycans by ADAMTS-4 reduces lamellar resistance to compression, thus exposing tensile elements of the ECM to excessive stretch and contributing to failure.

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Conclusion 

Lamellar proteoglycans are similar to those of articular cartilage and hence, likely to play a key role in maintaining lamellar integrity.