Alterations in tendon microenvironment in response to mechanical load: Potential molecular targets for treatment strategies

Mohamed B. Fouda, Finosh G. Thankam, Matthew F. Dilisio, Devendra K. Agrawal

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations


Rotator cuff (RC) tendons could beinflicted in many ways with an eventual outcome of pain, weakness and disability, which represent a large burden on health care cost. However, optimal healing, either conservatively or with surgical intervention, remains an issue that needs further investigation. Disorders of the RC tendons may result from external factors like trauma, or internal factors through physiologic and metabolic derangement. Most RC tendon disorders may be asymptomatic and may result from an over-activity of the inflicted shoulder and its tendons. Such tendon disorders are poorly diagnosed since patients do not seek medical attention until pain or weakness ensue. Immunological and biochemical events in RC disorders due to mechanical intolerance have not been investigated. Generally, the mechanical load drives normal physiological properties of the tendon. But, mechanical overload/burden exerts stress on tenocytes, and disrupts the tendon microenvironment by triggering a multitude of signaling pathways leading to extracellular matrix remodeling, disorganization, alteration in collagen composition and apoptosis. These events result in weak tendon which is highly susceptible to rupture or tear. In this article, we critically reviewed the intrinsic signaling pathways that are excessively triggered by continuous mechanical load and the counteracting physiological responses and associated derangements. The elucidation of the molecular events underlying mechanical stress-induced symptomatic/asymptomatic tendinopathy could provide information on potential target sites for translational application in the management of rotator cuff disorders.

Original languageEnglish (US)
Article numberAJTR0059913
Pages (from-to)4341-4360
Number of pages20
JournalAmerican Journal of Translational Research
Issue number10
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research


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