Mechanotransduction

You have an athlete with a stress fracture. The physician prescribes active rest and places the athlete in a non-weight bearing boot. Sound familiar? Suppose I told you the better option is to place some load on that bone and non-weight bearing is not recommended. Would you think I am nuts? Maybe I can convince you otherwise. Let me explain but, before you read the next paragraph and decide to leave the page, bear with me. What follows this introductory piece may provide insight to further understanding of injury pathophysiology and could revolutionize the future of rehabilitation science.

In January 2013 the Annals of Human Genetics published an article that demonstrated Achilles Tendinopathy is associated with gene polymorphism (Abrahams, et al., 2013). I am not a geneticist by any stretch of the imagination, so pardon my basic explanation. COL51A is a gene that encodes the development and organization of Type V collagen. Type V collagen is a collagen that is distributed in tissues as a component of extracellular matrix and composed of one pro alpha 2 (V) and two pro alpha 1 (V) chains. This collagen can be found in ligaments, tendons, and connective tissue. COL51A plays an integral role in development and maintenance of connective tissue. Abrahams, et al. (2013) demonstrated that polymorphisms occur in the COL51A gene causing altered structure of collagen resulting in tendionpathy.

I state the aforementioned because it is time for athletic trainers to begin taking a deeper look at pathophysiology and more importantly, to utilize this understanding in the development of our rehabilitation and treatment guidelines. Some of you may already be cognizant of this, but these revolutionary approaches to treatment and rehabilitation are already coming to light. Let me introduce the concepts of cellular signaling, mechanotransduction, and mechanotherapy.

Mechanotransduction and the Processes of:

Mechanotransduction ( described by Khan 2009) is the process whereby mechanical load initiates biochemical signals that leads to gene upregulation, protein synthesis and ultimately structural change (Khan 2009). Load causes perturbation to cells that initiates signaling pathways, where mRNA is sent to the endoplasmic reticulum for gene encoding. If you recall from college physiology, proteins are created by ribosomes following this transcription. These proteins are the new collagen and are extruded from the extracellular matrix and delivered to the damaged tissue. This is why eccentric training heals tendinopathy.

This process is not limited to damaged connective tissue. The mechanical load induces cellular signaling in all tissue – nervous, muscular, connective, bone and cartilage (Khan, 2009). In muscle, load stimulates upregulation of mechanogrowth factor and ultimately hypertrophy. Chrondrocytes are sensitive to load and are fed through load. Load applied to osteocytes deep within bone stimulates bone lining cells and facilitates healing to expedite fracture repair.

Review of cool supporting studies: 

Joseph, et al., (2012) stated that tendinopathic tendon is less stiff and loses ability to transfer energy. Joseph goes on to state that load creates a viscoelastic response in the Achilles tendon that increases stiffness and decreased hysteresis. Fragala et al., (2011) demonstrated leukocyte β2-adrenergic receptor expression changed in response to heavy resistance exercise. Flück, et al., (2008) evaluated tenascin-C,  a protein responsible for tissue remodeling that is expressed only in damaged tissue and regulated by mechanical load. They found that mice deficient of tenascin-C had diminished muscle tissue healing and conclude that tenascin-C is needed for reducing and healing of musculoskeletal injuries.

Scott, et al., (2008), demonstrated physiological load induces an osteogenic response that stimulates anabolic cellular activity in bone. In the Journal of Sport Rehabilitation – published by the one and only Human Kinetics – stated “the notion that deep friction massage may provide mechanical stimulation for healing is intriguing, especially given the context in which Cyriax, advocated this “mechanotherapy” as early as 1984…. While this is difficult to study in a human model, there is some poignant animal evidence that tendon massage indeed stimulates tissue adaptation at the cellular level.” (Joseph, et al., 2012). Durieux, et al., (2009) assessed regulation of focal adhesion kinase in mechano-regulated differentiation of slow-oxidative muscle. Focal adhesion kinase initiates cellular signaling and ultimately migration of cells and is required during development. The authors found that focal adhesion kinase is part of the signaling pathway that governs repair of striated muscle.

Conclusion:

Is a non-weight bearing walking boot the best treatment option for a stress fracture? It appears it is not. Based on the data discussed here, the practitioner must utilize an intricate balance between rest and mechanical loading of bone to obtain optimal healing. In order to heal damaged tissue we must use exercise as a repair stimulus – mechanotherapy.

The body of evidence exists and is continuing to grow. It is recommended athletic trainers and rehabilitation specialists take time to understand the pathophysiology of injury and the biochemical processes that elicits healing. In the very near future you will need to understand the biochemical events that promote tissue repair. The knowledge gained will dictate rehabilitation protocols needed for specific injuries.

References:

Abrahams Y, Laguette MJ, Prince S, and Collins M. Polymorphisms within the COL5A1 3′-UTR That Alters mRNA Structure and the MIR608 Gene are Associated with Achilles Tendinopathy. Ann Hum Genet. (Epub – ahead of print) Jan 2013.

Khan, K M, and Scott, A. Mechanotherapy: How Physical Therapists’ Prescription of Exercise Promotes Tissue Repair.  Br J Sports Med. 2009;43:247–251.

Joseph, MF, Lillie, KR, Bergeron, DJ, and Denegar, CR. Measuring Achilles tendon mechanical properties: A reliable, noninvasive method. J Strength Cond Res. 26(8): 2017–2020, 2012.

Fragala, M. S., Kraemer, W. J., Mastro, A. M., Denegar, C. R., Volek,  J. S., Hakkinen, K.,  Anderson, J.M.,  Lee, E. C., and Maresh, C. M. Leukocyte β2-Adrenergic Receptor Expression in Response to Resistance Exercise. Med. Sci. Sports Exerc. Vol. 43, No. 8, pp. 1422–1432, 2011.

Fluck M, Mund SI, Schittny JC, Klossner S, Durieux AC, et al. (2008) Mechano-regulated tenascin-C orchestrates muscle repair. Proc Natl Acad Sci U S A 105: 13662–13667.

Scott, A., Khan, K.M.,  Duronio, V, Hart, D.A. Mechanotransduction in Human Bone In Vitro Cellular Physiology that Underpins Bone Changes with Exercise. Sports Med. 2008; 38 (2): 139-160.

Joseph, MF, Taft, K, Moskwa, M, and Denegar, CR. Deep Friction Massage to Treat Tendinopathy: A Systematic Review of a Classic Treatment in the Face of a New Paradigm of Understanding. Journal of Sport Rehabilitation. 2012, 21, 343-353.

Durieux AC, D’Antona, G, Desplaches, D,  Freyssenet, D, Klossner, S, Bottinelli, R, and Fluck, M. Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype. Jof Physiol.  2009;587:14. 3703–3717.

11 thoughts on “Mechanotransduction

  1. Geoff

    Awesome post. You should look into the Fascia Distortion Model. Its deep manual therapy. I have seen immediate dramatic effects on range of motion and pain in both acute and chronic conditions.

    Reply
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