The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair.

Am J Pathol

Department of Biomedical Engineering, New York University Tandon School of Engineering, New York, New York; Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, New York. Electronic address:

Published: June 2024

AI Article Synopsis

  • Proinflammatory macrophages showed increased expression of RHAMM, and targeting HA/RHAMM interactions with a specific peptide reduced inflammation and boosted anti-inflammatory markers.
  • In a rabbit study, injections of this peptide during cartilage repair led to fewer proinflammatory macrophages and better healing than using HA alone.

Article Abstract

Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and receptor for hyaluronan-mediated motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and fibrotic processes. This study shows an increased expression of RHAMM in proinflammatory macrophages. Interfering with HA/RHAMM interactions using a 15-mer RHAMM-mimetic, HA-binding peptide, together with high-molecular-weight (HMW) HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in proinflammatory macrophages. HA/RHAMM interactions were interfered in vivo during the regeneration of a full-thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of 15-mer RHAMM-mimetic. HA-binding peptide together with HMWHA reduced the number of proinflammatory macrophages and increased the number of anti-inflammatory macrophages in the injured knee joint and greatly improved the repair of the cartilage defect compared with intra-articular injections of HMWHA alone. These findings suggest that HA/RHAMM interactions play a key role in cartilage repair/regeneration via stimulating inflammatory and fibrotic events, including increasing the ratio of proinflammatory/anti-inflammatory macrophages. Interfering with these interactions reduced inflammation and greatly improved cartilage repair.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156159PMC
http://dx.doi.org/10.1016/j.ajpath.2024.01.020DOI Listing

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