Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases

The natural aging process and various pathologies correlate with alterations in the composition and the structural and mechanical integrity of the connective tissue. Collagens represent the most abundant matrix proteins and provide for the overall stiffness and resilience of tissues. The structural...

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Bibliographic Details
Published in:Matrix biology 2018-01, Vol.65, p.30-44
Main Authors: Panwar, Preety, Butler, Georgina S., Jamroz, Andrew, Azizi, Pouya, Overall, Christopher M., Brömme, Dieter
Format: Article
Language:English
Subjects:
Advanced glycation products
Advanced glycosylation end products
Aging
Cartilage
Cathepsin K
Cathepsins
Collagen
Collagenase
Extracellular matrix
Fibers
Glycosaminoglycans
Glycosylation
Matrix metalloproteinases
Mechanical properties
Mineralization
Proteolysis
Skin
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Summary:The natural aging process and various pathologies correlate with alterations in the composition and the structural and mechanical integrity of the connective tissue. Collagens represent the most abundant matrix proteins and provide for the overall stiffness and resilience of tissues. The structural changes of collagens and their susceptibility to degradation are associated with skin wrinkling, bone and cartilage deterioration, as well as cardiovascular and respiratory malfunctions. Here, matrix metalloproteinases (MMPs) are major contributors to tissue remodeling and collagen degradation. During aging, collagens are modified by mineralization, accumulation of advanced glycation end-products (AGEs), and the depletion of glycosaminoglycans (GAGs), which affect fiber stability and their susceptibility to MMP-mediated degradation. We found a reduced collagenolysis in mineralized and AGE-modified collagen fibers when compared to native fibrillar collagen. GAGs had no effect on MMP-mediated degradation of collagen. In general, MMP digestion led to a reduction in the mechanical strength of native and modified collagen fibers. Successive fiber degradation with MMPs and the cysteine-dependent collagenase, cathepsin K (CatK), resulted in their complete degradation. In contrast, MMP-generated fragments were not or only poorly cleaved by non-collagenolytic cathepsins such as cathepsin V (CatV). In conclusion, our data indicate that aging and disease-associated collagen modifications reduce tissue remodeling by MMPs and decrease the structural and mechanic integrity of collagen fibers, which both may exacerbate extracellular matrix pathology. •Aging-associated modifications of collagen such as mineralization and AGE-modification reduce susceptibility toward MMPs.•Removal of collagen-associated glycosaminoglycans only affect collagenolysis by cathepsin K but not by MMPs.•Only cathepsin K but not non-collagenolytic cathepsins can finalize MMP-initiated collagen degradation.•Mechanical stability of aged collagens is reduced after MMP exposure.•Aging-associated modifications of collagen likely contribute to the pathology of diseases and general aging processes.
ISSN:0945-053X
1569-1802
DOI:10.1016/j.matbio.2017.06.004