MICRORNAS IN SKELETAL DEVELOPMENT (A DELANY, SECTION EDITOR) Disease-Specific MicroRNAs Regulating Extracellular Matrix and Matrix Metalloproteinases in Tendinopathy Thomas M. Munro 1 & Finosh G. Thankam 1 & Matthew F. Dilisio 2 & R. Michael Gross 2 & Chandra S. Boosani 1 & Devendra K. Agrawal 1 # Springer Nature Switzerland AG 2018 Abstract Purpose of Review Specific differences in the altered molecular mechanisms between healthy tendon tissues and tendinopathy- afflicted tendon largely correlate with increase in collagen type III and a decrease in collagen type I. The canonical IL-1R- mediated inflammation, the TGF-β/Smad signaling, and JAK/STAT pathways have been implicated as important regulatory pathways in tendinopathy. In addition, recent analysis of the pathologically induced gene expression in tendinopathies has identified a clear role of microRNAs (miRNAs) in suppressing the expression of specific genes and their pathways during the progression of the disease. Recent Findings Research on miRNAs and the pathways downstream signaling in tendinopathy have shown that several miRNA families influence the molecular pathology associated with tendinopathy, but the exact mechanism in which this occurs still remains to be determined. Identification of the expression or repression of miRNAs which regulate different cellular pathways is critical not only to understand the molecular mechanisms but also to assist in identifying the inter-regulatory pathways in the diseased conditions. In addition to the primary focus to delineate the role of miRNA-29 family in tendinopathy, which is prominently featured in this manuscript, alternate microRNAs could play a role in tendinopathy. Summary Determining the intricacies of how these miRNAs influence the pathways of tendinopathy provides vital clues for alternate possible targets which is critical to the development of future therapeutics to treat tendinopathy. Keywords Tendinopathy . MicroRNA . IL-33 . TGF- β . Smad . JAK/STAT pathway . Collagen synthesis . Matrix metalloproteinases Introduction Tendinopathy encompasses a spectrum of tendon-related dis- orders that are characterized by movement-related pain and musculo-skeletal dysfunction. The alterations of the usage of the terms tendinitis, tendinosis, and tendinopathy to describe this pain exemplify the scientific field’s historical disagree- ment on this clinical syndrome. The progress in the under- standing of the pathology changed the descriptive word for defining tendinopathy [1]. Tendinitis was the word of choice used in this diagnosis until a paradigm shift began to occur in the 1990s. Several groups started to question whether inflam- mation played a major role in the pathology of this disease. Various articles emerged which described the lack of inflam- matory infiltrate in chronic as well as acute instances of tendon-related injuries [1–3]. The use of tendinitis, a term indicating the presence of inflammation, to describe activity- related tendon pain fell out of favor, while the use of tendinosis rose in popularity. The understanding of the pathology of this disease contin- ued to evolve throughout the twenty-first century, and the scientific community began to revisit the role inflammation played in this movement-related tendon pain disorder. Questions began to be asked whether perhaps it was going This article is part of the Topical Collection on MicroRNAs in Skeletal Development * Devendra K. Agrawal dkagr@creighton.edu 1 Department of Clinical & Translational Science, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178, USA 2 Department of Orthopedic Surgery, Creighton University Medical Center, 7710 Mercy Road, Omaha, NE 68124, USA Current Molecular Biology Reports https://doi.org/10.1007/s40610-018-0103-0