title: Biomimetic aggrecan reduces cartilage extracellular matrix from degradation and lowers catabolic activity in ex vivo and in vivo models.
abstract: Aggrecan, a major macromolecule in cartilage, protects the extracellular matrix (ECM) from degradation during the progression of osteoarthritis (OA). However, aggrecan itself is also susceptible to proteolytic cleavage. Here, the use of a biomimetic proteoglycan (mAGC) is presented, which functionally mimics aggrecan but lacks the known cleavage sites, protecting the molecule from proteolytic degradation. The objective of this study is to test the efficacy of this molecule in ex vivo (human OA synovial fluid) and in vivo (Sprague-Dawley rats) osteoarthritic models. These results indicate that mAGC's may protect articular cartilage against the loss of key ECM components, and lower catabolic protein and gene expression in both models. This suppression of matrix degradation has the potential to provide a healthy environment for tissue repair.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907.
authors.forename: Shaili
authors.initials: S
authors.lastname: Sharma
authors.forename: Aeju
authors.initials: A
authors.lastname: Lee
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Inchan
authors.initials: I
authors.lastname: Youn
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Trippel
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000494:pharmacology*; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002417:Cattle; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D002809:Chondroitin Sulfates / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053674:Aggrecans; D016207:Cytokines; D018836:Inflammation Mediators; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D053509:Matrix Metalloproteinase 13
keywords: aggrecan; biomimetics; cartilage; extracellular matrix; proteolytic enzymes