The Content and Size of Hyaluronan in Biological Fluids and Tissues

Abstract

Hyaluronan is a simple repeating disaccharide polymer, synthesized at the cell surface by integral membrane synthases. The repeating sequence is perfectly homogeneous, and is the same in all vertebrate tissues and fluids. The polymer molecular mass is more variable. Most commonly, hyaluronan is synthesized as a high-molecular mass polymer, with an average molecular mass of approximately 1000–8000 kDa. There are a number of studies showing increased hyaluronan content, but reduced average molecular mass with a broader range of sizes present, in tissues or fluids when inflammatory or tissue-remodeling processes occur. In parallel studies, exogenous hyaluronan fragments of low-molecular mass (generally, <200 kDa) have been shown to affect cell behavior through binding to receptor proteins such as CD44 and RHAMM (gene name HMMR), and to signal either directly or indirectly through toll-like receptors. These data suggest that receptor sensitivity to hyaluronan size provides a biosensor of the state of the microenvironment surrounding the cell. Sensitive methods for isolation and characterization of hyaluronan and its fragments have been developed and continue to improve. This review provides an overview of the methods and our current state of knowledge of hyaluronan content and size distribution in biological fluids and tissues.

Activity of two hyaluronan preparations on primary human oral fibroblasts

“…The investigated HA preparations appear close to the physiological HA that is found in many biological fluids and solid tissues and is reported to possess an average MW of approximately 1000‐6000 kDa . Little if any HA below 1000 kDa is found in healthy solid tissues .…”

Brain extracellular space, hyaluronan, and the prevention of epileptic seizures

“…There is hope that a treatment will be developed which can be administered during the latent period which would stop the process of epileptogenesis and prevent the onset of spontaneous seizures. In analyzing results that suggest that HA may be epileptogenic or antiepileptogenic, it is worth pointing out that the scientific community is lately becoming increasingly aware that both high- and low-molecular-weight HA have biological effects, that those effects are often not the same, and that some studies measuring changes in HA content have not differentiated between HA of different sizes (Cowman et al, 2015; Sherman et al, 2015). …”

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

“…HA regulates proliferation and differentiation of Sox2 + NS/PCs through the CD44 receptor . In inflammatory environments, high molecular weight HA acts as a scavenger of damaging free radical species . HA hydrogels can be modified to provide additional matrix‐derived functionalities, such as integrin‐binding and mechanical cues, in combination .…”