Cluster of differentiation 44 (CD44) receptor (CD44)

Cluster of differentiation 44 (CD44) receptor is a ubiquitous transmembrane glycoprotein that serves as the primary cell-surface receptor for hyaluronan, a major component of the extracellular matrix [1]. It is highly expressed on mesenchymal stem cells (MSCs), where it serves as a defining marker and facilitates their homing to sites of injury, and on joint cells such as chondrocytes and synoviocytes [3, 4]. In the context of joint health, CD44-hyaluronan interactions are critical for maintaining the structural integrity of articular cartilage and modulating inflammatory responses [5]. Dysregulation of CD44 is linked to the progression of osteoarthritis and rheumatoid arthritis, as well as various cancers where it promotes metastasis and chemoresistance [2]. Therapeutic strategies targeting CD44 include the administration of exogenous hyaluronan to restore joint lubrication and signaling, as well as the development of monoclonal antibodies to inhibit its pathological activity [2, 5]. However, the widespread expression of CD44 across diverse tissues presents a significant challenge for achieving target specificity and avoiding off-target effects [1].

Other names

H-CAMPgp-1Hermes antigenExtracellular matrix receptor IIIHUTCH-IPhagocytic glycoprotein 1LHRMDU2MDU3MIC4CDw44CSPG8

CD44 functions as the primary receptor for hyaluronan (HA). Upon binding HA, CD44 undergoes conformational changes and clustering, which triggers intracellular signaling cascades including the Ras-MAPK and PI3K-Akt pathways, as well as cytoskeletal rearrangements via RhoGTPases [1, 2]. In joint cells, this interaction helps maintain cartilage homeostasis and inhibits apoptosis, while in MSCs, it mediates adhesion to the endothelium and migration into damaged tissues [3, 4].