Why consider topical Sodium Hyaluronate (HA) in the treatment of tendinopathy?
Firstly, the difference between HA and other glycosaminoglycans is that it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large, with its molecular weight often reaching the millions. HA is considered to be a key molecule in the tissue regeneration process. It has been shown to modulate via specific HA receptors, inflammation, cellular migration, and angiogenesis, which are the main phases of wound healing.
In relation to tendinopathies, hyaluronic acid modulates a variety of cellular functions: anti-inflammatory activity, enhanced cellular proliferation and collagen deposition. Studies have shown a link between the inhibition of fibroblast proliferation, with a reduction in the formation of adhesions at the tendon healing site; by limiting the proliferation of fibroblasts, HA may reduce the risk of adhesions.
It has sometimes been assumed, in relation to tendinopathic change, that because there is an excess of GAGs detectable within the local bio-chemical environment, there is an excess of hyaluronan, which is not necessarily the case. For example, the activity of hyaluronidase (enzymes that catalyse the degradation of hyaluronan) has been shown to increase during the healing of equine superficial digital flexor tendon injuries.
Multiple studies analysing tendon healing have confirmed that HA reduces the formation of scars and granulation tissue, and also prevents adhesions. Importantly, HA forms part of the extracellular matrix as a major component of ground substance, giving structure for other GAGs and proteoglycans. In tendon healing, the GAGs provide a temporary structure in the early stages of the wound. So without the presence of HA, there is evidence to suggest that other GAGs are of limited use. Also, high levels of HA are thought to be instrumental in scar-less healing by facilitating the movement and proliferation of fibroblasts, and by regulating the production and type of collagen.
HA also plays an important role as a hydrating agent, being able to absorb 3,000 times its own weight in water. HA appears to inhibit the expression of key intermediaries for the inflammatory signalling pathways (NF-kB), by reducing the expression of pro inflammatory factors, exogenous HA may reduce the fragmentation of endogenous HA and further stimulate synthesis of endogenous HA..
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