Hypoxia: a Critical Regulator of Early Human Tendinopathy
Reference: Millar NL, Reilly JH, Kerr SC, Campbell AL, Little KJ, Leach WJ, Rooney BP, Murrell GAC, McInnes IB. Hypoxia: a critical regulator of early human tendinopathy. Annals of the Rheumatic Diseases. 17(1): 302-310, 2012.
Scientific Literature Review
Reviewed By: W Drew Chapman, DPM
Residency Program: Grant Medical Center
Tendinopathy is quite common in the lower extremity and is seen in practice on almost a daily basis. A hypoxic environment can present in the lower extremity in cases such as peripheral arterial disease. This study provided insight on how hypoxia affects tenocytes in regards to inflammation, apoptosis, and collagen formation at the molecular level.
Samples of torn supraspinatus tendon were harvested during repair which represented established pathology, and were matched to intact subscapularis which represented early pathology. Control samples were harvested from patients undergoing stabilization with no history of pathology. Markers for hypoxia, inflammation, and apoptosis were quantified by immunohistochemical techniques. Human tenocytes were derived from hamstring tendon tissue and were grown under normoxic (21 percent) and hypoxic (1 percent) conditions. Samples were also analyzed for apoptotic-related proteins, and immunohistochemically stained for collagen typing.
The subscapularis tendon, which represented early tendinopathy, had statistically greater staining for inflammatory markers as well as presence of inflammatory cells including macrophages, mast cells, and T cells compared to the torn tendon (late pathology) and the control. The torn supraspinatus tendons showed a greater composition of collagen type III when compared to the controls, which is a hallmark feature of tendinopathy as normal tendon composition is collagen type I. The tenocytes grown in hypoxic conditions had a significantly greater number undergoing apoptosis expression of apoptotic markers when compared to cells in normoxic environment. The cells in the hypoxic environment showed upregulation of collagen type IIIA mRNA and a decrease in collagen type IA mRNA which was also demonstrated through immunohistological analysis.
Hypoxia promotes an increase in proinflammatory products, apoptosis, and drive the cell to synthesize collagen type III. Hypoxia is likely a critical component in early tendinopathy. This study also provides insight into the etiology of tendon disorders and new avenues for therapeutic modalities.