Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of 
disability in middle-aged individuals affected by nontraumatic shoulder 
dysfunctions. Our previous studies have demonstrated that four different 
hyaluronic acid preparations (HAPs), including Artrosulfur® hyaluronic acid (HA) 
(Alfakjn S.r.l., Garlasco, Italy), may exert a protective effect in human 
RCT-derived tendon cells undergoing oxidative stress damage. Recently, 
methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have 
anti-inflammatory properties and to cause pain relief in patients affected by 
tendinopathies. This study aims at evaluating three preparations (Artrosulfur® 
HA, MSM, and Artrosulfur® MSM + HA) in the recovery from hydrogen 
peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, 
Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) 
and prostaglandin E2 (PGE2) modulation were investigated. In parallel, 
expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I 
and III were also examined. Results demonstrate that Artrosulfur® MSM + HA 
improves cell escape from oxidative stress by decreasing cytotoxicity and by 
reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 
and MMP14 levels and enhances collagen III expression after 24 h, proteins 
globally related to rapid acceleration of the extracellular matrix (ECM) 
remodelling and thus tendon healing. By improving the anti-cytotoxic effect of 
HA, the supplementation of MSM may represent a feasible strategy to ameliorate 
cuff tendinopathies.