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
I think this is an interesting topic as I don't know all that much about joint contractures. In my limited amount of experience, I have not had an personal encounters aside from the observations that I made at a physical therapy clinic. Joint contractures is definitely something to keep in mind when setting up rehabilitation plans especially for someone who does not plan to return to the same physical condition because their competitive season is over. I would be interested in seeing more research in this area, but I can see how it would be hard to do the research on humans as there would be a potential harmful side effect.
I think that the authors come to some good conclusions and I appreciate the basic science nature of this article. It gives good insight into what is truly occurring at the metabolic level in these somewhat mysterious and challenging injuries. I think that where a large issue originates from is the fact that some of the most common joint contractures originate in the general public. By the time a patient from this population recognizes they have an issue, schedules an appointment, is able to get in and see their physician, be referred to a physical therapist or other healthcare professional and begin treatment, it is already past this stage. Something that could be beneficial to these patients would be having some preemptive coaching. If around the age at which issues like Dupuytren’s and frozen shoulder become more common, the healthcare professional educated the individual a bit on these conditions, they may have a slightly decreased threshold to report their symptoms. In joint contractures more commonly seen in sports medicine I think it solidifies our practices of early mobilization and movement. I must admit I was especially excited to see this article pop up since my brother (Dr. Jon Barlow) is one of the authors. We had a great discussion about it over Thanksgiving dinner! Thanks for the write up!
Speaking from clinical experience, I had patients with adhesive capsulitis that had poor attendance (showing once a week instead of the scheduled three times a week). Due to this, I always felt like their time in clinic was than optimal since one treatment a week was not going to help as much as we needed it, so progression was slow at best. This study really offered me hard evidence on the initial stages of rehabilitation in these conditions. And I'm happy that this study gives me a method to tell patients how important this phase is.
Thanks for this great post!
Shandi thanks for the comment. I agree it is difficult to conduct these studies on humans and therefore may require more animal model studies in the hopes that they can translate clinically.
Greg thanks for the comment. I agree early identification is key but could be difficult. In a sports medicine setting it might be easier but is less common in younger athletes. We can only hope that patients seek out medical attention sooner than later. Thats great that your bother is an author. Would he be interested in commenting and giving further insight?
Jay thanks for the comment. Yes, it seem like many other conditions that early motion is important to combat the joint contracture. I am wondering if myofibroblasts can be the cause for a lot of joint stiffness we see at other joints. Something to think about.