{"id":4566,"date":"2025-12-11T19:48:08","date_gmt":"2025-12-12T00:48:08","guid":{"rendered":"https:\/\/www.bu.edu\/mechanobiology\/?page_id=4566"},"modified":"2025-12-11T20:33:29","modified_gmt":"2025-12-12T01:33:29","slug":"poster-presentation-bor-lin-huang","status":"publish","type":"page","link":"https:\/\/www.bu.edu\/mechanobiology\/poster-presentation-bor-lin-huang\/","title":{"rendered":"Poster Presentation: Bor-Lin Huang"},"content":{"rendered":"<p class=\"p2\"><strong>ABSTRACT<\/strong><\/p>\n<p class=\"p2\"><b>Targeted Inhibition of Pathogenic TGF-\u03b2<\/b>\u00a0<b>Activity in Arthrofibrosis via Non-Cartilage-Permeating Antagonists <\/b><b><\/b><\/p>\n<p class=\"p3\">Bor-Lin Huang<span class=\"s2\">1<\/span>, Satviki Singh<span class=\"s2\">1<\/span>, Sedat Dogru<span class=\"s2\">1<\/span>, Thomas P. Schaer<span class=\"s2\">2<\/span>, Brian D. Snyder<span class=\"s2\">1<\/span>, Matthew D. Layne <span class=\"s2\">3<\/span>, Mark W. Grinstaff<span class=\"s2\">1<\/span>, Michael B. Albro<span class=\"s2\">1 <\/span><\/p>\n<p class=\"p3\"><span class=\"s2\">1 <\/span>College of Engineering, Boston University, MA <span class=\"s2\">2 <\/span>Department of Clinical Studies New Bolton Center, University of Pennsylvania, PA <span class=\"s2\">3 <\/span>Chobanian and Avedisian School of Medicine, Boston University, MA<\/p>\n<p class=\"p2\"><b>Objectives: <\/b>Arthrofibrosis (AF) is a debilitating fibrotic disorder of the diarthrodial joint synovium, leading to pain and limited joint motion. AF primarily initiates from TGF-\u03b2 dysregulation in synovial fluid (SF) in aging or in the aftermath of trauma or surgery. Prior intra-articular drug therapies to inhibit pathogenic SF TGF-\u03b2 have achieved limited success, encumbered by off-target inhibition of beneficial TGF-\u03b2 in articular cartilage, leading to cartilage degeneration. Here, we propose a targeted therapeutic approach using non-cartilage-permeating inhibitors (NCPIs) which selectively inhibit pathogenic TGF-\u03b2 in SF during arthrofibrosis while avoiding off-target inhibition of beneficial TGF-\u03b2 signaling in articular cartilage. We evaluate the use of large, anionic TGF-\u03b2 receptor (SolR) antagonist proteins, which possess high affinity to neutralize TGF-\u03b2 in SF and show limited penetration into cartilage due to steric\/electrostatic partitioning from the dense sulfated-glycosaminoglycan-rich cartilage EC.<\/p>\n<p class=\"p2\"><b>Materials and Methods: <\/b>The efficacy of two NCPIs (recombinant TGF-\u03b2 type-II and type-III soluble receptors; SolR2 and SolR3) and a small-molecule cartilage-permeating inhibitor (CPI) (LY364947) to selectively inhibit pathogenic TGF-\u03b2 in SF was assessed via an in vitro co-culture system consisting of bovine cartilage explants and synoviocyte-seeded collagen construct, allowing for simultaneous monitoring of TGF-\u03b2-induced synovium contraction (a surrogate measure of fibrosis) and off-target effects on cartilage mechanical properties.<\/p>\n<p class=\"p2\"><b>Results: <\/b>Pathogenic TGF-\u03b2 levels induced 70% contraction of synoviocyte-seeded constructs (p&lt;0.05), relative to TGF-\u03b2-free. LY364947 significantly reduced synovium contraction to 8%, relative to TGF-\u03b2-free, and induced a significant 60% reduction in cartilage Young\u2019s modulus (E<span class=\"s3\">Y<\/span>) (p&lt;0.05). In contrast, SolR2 and SolR3 reduced synovium contraction to 18.5% and 49%, respectively (p&lt;0.05) and had no off-target effect on cartilage EY, thus supporting NCPI selective inhibition of pathogenic TGF-\u03b2 in SF.<\/p>\n<p class=\"p2\"><b>Conclusion: <\/b>Non-cartilage-permeating antagonists represent a novel pharmacological approach for inhibiting pathogenic TGF-\u03b2 in arthrofibrosis while minimizing the off-target effects on articular cartilage.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>ABSTRACT Targeted Inhibition of Pathogenic TGF-\u03b2\u00a0Activity in Arthrofibrosis via Non-Cartilage-Permeating Antagonists Bor-Lin Huang1, Satviki Singh1, Sedat Dogru1, Thomas P. Schaer2, Brian D. Snyder1, Matthew D. Layne 3, Mark W. Grinstaff1, Michael B. Albro1 1 College of Engineering, Boston University, MA 2 Department of Clinical Studies New Bolton Center, University of Pennsylvania, PA 3 Chobanian and [&hellip;]<\/p>\n","protected":false},"author":14358,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4566"}],"collection":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/users\/14358"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/comments?post=4566"}],"version-history":[{"count":2,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4566\/revisions"}],"predecessor-version":[{"id":4569,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4566\/revisions\/4569"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/media?parent=4566"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}