Expression and activity of collagenases in the digital laminae of horses with carbohydrate overload-induced acute laminitis.
Authors: Wang L, Pawlak E A, Johnson P J, Belknap J K, Alfandari D, Black S J
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary: Matrix Metalloproteinase Expression in Laminitis Carbohydrate overload-induced laminitis involves progressive degradation of the laminar extracellular matrix, but the enzymatic mechanisms driving this destruction remain incompletely understood; Wang and colleagues investigated whether matrix metalloproteinases (MMPs)—a family of tissue-degrading enzymes—are upregulated in affected laminae and contribute to structural failure. Using real-time PCR, Western blotting, and immunofluorescent microscopy, they compared gene expression, protein levels, and spatial distribution of specific collagenases (MMP-1 and MMP-13) in laminae from healthy horses and those with carbohydrate overload laminitis at various stages of lameness severity. Only MMP-1 and MMP-13 genes were significantly upregulated in laminitic horses, with MMP-13 expression correlating specifically with severe (Obel grade 3) lameness and appearing in both pro- and enzymatically active forms; critically, MMP-13 localised to the basal epithelium of secondary epidermal laminae, and its increased activity corresponded with the appearance of discrete regions in the secondary dermal laminae that were depleted of collagen I, fibronectin, and glycosaminoglycans. These findings suggest that MMP-13 activation is a key pathological feature of severe laminitis and may directly cause the focal matrix degradation and structural failures observed clinically. For practitioners, this research strengthens the rationale for therapeutic strategies targeting enzymatic degradation—such as matrix metalloproteinase inhibitors or anti-inflammatory approaches that suppress MMP activation—during the acute phase of laminitis when intervention is most critical.
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Practical Takeaways
- •Carbohydrate overload triggers specific MMP activation that progressively degrades the laminar attachment; this provides a mechanistic explanation for acute laminitis development and progression to severe lameness grades.
- •MMP-13 is a key enzyme involved in structural failure of the laminae, suggesting that therapeutic strategies targeting MMP activity or carbohydrate management timing could be critical for preventing progression from early to severe laminitis.
- •Understanding that laminar failure involves active enzymatic degradation of the extracellular matrix reinforces the importance of rapid intervention and dietary management in early laminitis cases before irreversible structural damage occurs.
Key Findings
- •MMP-1 and MMP-13 genes were upregulated in carbohydrate overload-induced laminitis, with MMP-1 at Obel grade 1 and MMP-13 at Obel grade 3 lameness.
- •MMP-13 localized to basal epithelium of secondary epidermal laminae and appeared in processed form (48 kDa) alongside pro-enzyme (61 kDa).
- •Increased MMP-13 expression correlated with appearance of ECM-free lesions in secondary dermal laminae lacking collagen I, fibronectin, and glycosaminoglycans.
- •MMP-13 activity likely contributes to ECM degradation and formation of gaps or tears in laminar tissue during OG3 lameness.