Myofibroblast cells are preferentially expressed early in a rabbit model of joint contracture.

Abdel MP, Morrey ME, Barlow JD, Kreofsky CR, An KN, Steinmann SP, Morrey BF, Sanchez-Sotelo J.  J Orthop Res. 2011 Nov 4. doi: 10.1002/jor.21588. [Epub ahead of print]

Joint contractures in orthopaedics and sports medicine have been a very challenging condition to treat.  Two of the most commonly seen contractures are adhesive capsulitis and Dupuytren’s contracture.  These conditions cause large decreases in range of motion and joint stiffness which ultimately lead to severe limitation in function.  Myofibroblasts is a type of fibroblast that expresses α-smooth muscle actin and has been shown to be present in capsule contractures.  However, the temporal expression of myofibroblasts in joint contractures is unknown.  Therefore, Abdel et al. aimed to determine the absolute and relative number of myofibroblasts in contracting joint capsules over time and compared to the contralateral limb and a non-operative control animal. They used 18 New Zealand White female rabbits divided between three groups:  Group I (2 weeks immobilization), Group II (8 weeks immobilization), and Group III (8 weeks of immobilization plus 16 weeks of remobilization).  Their model for joint contraction consisted of a surgical trauma (excision of the cruciate ligaments and hyperextension) followed by immobilizing the knee at 160° of knee flexion using K-wire.  The contralateral limb was not manipulated in anyway.  Control animals were also used for comparison with no manipulation of either limb.  For the remobilization group the rabbits underwent a second surgery to remove the K-wire.  Once the study was completed the posterior capsule of the knee was removed and processed for immunohistochemistry to identify the presence and amount of myofibroblasts.  They found a significantly larger numbers of myofibroblasts in the operated limbs at 2 weeks compared to the contralateral, and the control limbs.  However, there was a significant reduction in myofibroblasts between the 2-week time point and the 8-week time point in the operative limbs. After 8 weeks of immobilization or after 16 weeks of remobilization there were no significant differences to the control limbs.    

This was a very interesting study which begins to lead the way in understanding the pathomechanics of joint contracture.  They found that myofibroblasts are more highly expressed in a joint contracture model although the expression is temporal.  This suggests that myofibroblasts are only active during the early stages of the development of joint contracture.  This is important in understanding and developing treatment strategies for these patients as there may be a short window of time to counteract these conditions.  However, the mechanism sill remains unknown.  In my mind there are two possible scenarios that may be occurring.  First, the authors describe that the large tension during the initial injury may activate myofibroblasts which lead to joint contracture.  Second, many conditions like frozen shoulder occur without an initial injury, therefore a lack of tension or motion may activate myofibroblasts to remodel the capsule to a new contracted state.  If both mechanisms occur then rehabilitation may need to incorporate low level joint mobilizations to minimize the expression of myofobroblasts by reducing capsule tension and also preventing a state of no tension.  Additional research is required to determine the true mechanisms of joint contracture but research like this is just the tip of the iceberg.  What are your thoughts on the role of myofibroblasts in the development of joint contractures and your strategy for rehabilitation? 

Written by:  Stephen Thomas
Reviewed by: Jeffrey Driban 

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Abdel MP, Morrey ME, Barlow JD, Kreofsky CR, An KN, Steinmann SP, Morrey BF, & Sanchez-Sotelo J (2011). Myofibroblast cells are preferentially expressed early in a rabbit model of joint contracture. Journal of Orthopaedic Research PMID: 22057979