Biomechanical and Molecular Factors in Enthesis-Related Disorders: Perspectives on Patterns in Tendinopathy and Ankylosing Spondylitis
Alfonse T. Masi 1, Brian Andonian 1, Kristina Prus 1, Kalyani Nair 2
1Department of Medicine, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, Il 61656, USA, Tel: +1-309-671-8428, Fax: +1-309-671-8513, Email:
2 Department of Mechanical Engineering, Bradley University, 1501W. Bradley Ave., Peoria, Il, 61625, Tel; +1-309-677-4562, Fax: +1-309-677-3453, Email:
BACKGROUND Musculoskeletal fibrous connective tissue structures (tendon, ligament, and fascia) link muscles to bony framework and are enclosed in extracellular matrix (ECM). An enthesis [G. an, insertion + thesis, a placing] is a specialized organ of fibrous tissues attaching to bone. Entheses may be damaged by degenerative (-pathy, G. disease) or inflammatory (-itis, L.) processes. Mechanical overloading can lead to tendinopathy (TP), but inflammatory mechanisms are universally emphasized to cause ankylosing spondylitis (AS). This review examines biomechanical influences in TP and AS to guide earlier clinical management.
METHODS Literature on biomechanical, biomolecular, clinical, histological, immunological, and pathological aspects of TP and AS were reviewed. The aim was to compare mechanistic processes in these disorders for a better understanding of risk factors and more effective therapy.
RESULTS Enthesis connective tissues in TP and AS show dense collagen fiber organization, which is mechanically-linked in ECM, containing macromolecular proteoglycans, cytokines, proenzymes, and growth factors. The entheseal microanatomy is adapted to functional demands of mechanical loading, force transmissions, tensional, and compressional stress concentrations at the tissue interfaces. Earlier and later stage TP lesions are interpreted to be adaptive as well as healing reactions to mechanical overloading. Histopathology may include myxoid degeneration, remodeling reactions, and vascularization, with new bone formations (enthesophytes) in more chronic TP. Inflammatory cell infiltrates are rarely observed.
In AS, high stress concentration occurs at the spinal entheses, where intervertebral annulus fibrosus disc fibers attach to the margins of vertebral body endplates. Mechanobiological pathways have not been studied in early AS nor the early histology [1]. The late entheseal lesions show erosion of cortical bone, neovascularization, and variable cellular infiltration, which are universally interpreted as inflammatory processes. Angiogenesis occurs in a mechanically dynamic environment, including cytokine, enzyme, and growth factor release from ECM [2]. Accordingly, mechanotransduction can induce neovascularization and inflammatory tissue reactions. The review yielded an integrated construct of the complex overlapping mechanobiology and molecular biology pathways (graphic to be shown).
CONCLUSION The literature review supports the concept that mechanical overloading occurs in both disorders. However, chronicity and intensity of the biomechanical processes, progressive structural damage, immunological, and genetic predisposition may lead to inflammation in AS. These new concepts may help in earlier, effective physical therapy approaches for TP and AS.
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J Rheumatol 2011;38: (in press)
[2] Shiu Y-T, Weiss JA, Hoying JB, et al. The role of mechanical stresses in angiogenesis. Crit Rev Biomed Eng 2005;33:431-510