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SP0121 Joint Homeostasis: Limitations and Advantages for Cartilage Repair in Oa
  1. D. Saris1,2
  1. 1Reconstructive Medicine, University Twente, Enschede
  2. 2Orthopedics, UMC Utrecht, Utrecht, Netherlands

Abstract

Traumatic joint damage, articular cartilage, the challenge of OA and the research into methods of restoring the articulation are not new topics of interest. For centuries, clinicians have recognized the importance of cartilage damage and sought ways of learning about the normal form and function of hyaline cartilage as well as the process of degradation and restoration. More recently, regenerative medicine was introduced as a method of restoring tissue or organ function, and has already been applied to cartilage repair. The possibility of modulating cells and tissues and applying this novel capability towards the restoration of musculoskeletal function provides great promise and opportunity for progress in orthopedics and traumatology.

An articulating joint has a complex design with many essential components and a multitude of interactions between structures such as synovium, cartilage, menisci, synovial fluid, ligaments and subchondral bone. These anatomical structures are influenced by factors such as motion, loading, alignment, weight, age, hormonal influences and many more. It is evident that this complex environment must be rigorously regulated. Furthermore, metabolic control must be flexible because the external environment of cells is not constant. Studies of a wide range of organisms have shown that there are a number of mechanisms for the control of physiological equilibrium, also referred to as Homeostasis. Vogel suggests that “the crux of a feedback system is the ability to adjust what it does, depending on conditions outside itself, where those conditions include the result of its own actions. In a strictly mechanical and formal sense, it has self-awareness.” We feel that the basic scientific concept of homeostasis should be implemented in our thinking when addressing the clinical problem of restoring a damaged articulation. With normal Joint Homeostasis, we mean the stable equilibrium of synovium and cartilage matrix void of inflammatory response in a well functioning articulation. When joint homeostasis is disturbed, this equilibrium is changed, and a myriad of intra-articular factors, such as inflammatory, molecular, or cellular components, come into play. Regulatory pathways are typically aimed at restoring equilibrium to normal homeostasis. However, in an articulation the initiation of a cascade of change such as in degenerative osteoarthritis will eventually irreversibly change the joint.

Homeostasis and cartilage defects As mentioned before, the majority of patients have a longer history of complaints before they are treated for their joint damage. For instance, effusion, pain and locking clearly signify that some degree of synovitis and matrix degradation is present. Thus, a disturbed local environment exists that provides a condition quite different from that in the undamaged, healthy joint. This altered intra-articular environment constitutes a change in joint homeostasis and could provide an explanation for the discrepancy between reproducible basic scientific data and promising in vivo examples of cartilage repair, and the variable clinical results reported in current literature. In joints with disturbed homeostasis, the local environment in which we try to achieve cartilage formation is considerably different from those with normal homeostasis

As fish do not thrive in a dirty aquarium, it is our responsibility to clean the tank.

The full extent of altered joint homeostasis cannot be examined effectively in a controlled environment since these conditions only mimic part of the natural organism and not all of the intricate regulatory functions are reproduced.

Following the approach suggested by our Concept of Joint Homeostasis, not only the damaged cartilage surface needs to be treated, but rather the entire joint will be the target of our regenerative approach attempt. This would imply also addressing synovitis, meniscal damage, ligament stability, limb alignment, and normalizing metabolic activity. Establishing true biological joint reconstruction might be of great importance for a large, mostly young, patient population for whom currently no reliable treatment exists.

Disclosure of Interest D. Saris Grant/Research support from: Tigenix, Sanofi, Smith & Nephew, Consultant for: Smith & Nephew, Conflict with: Tigenix, Sanofi, Conflict with: Smith & Nephew, Sanofi, Tigenix

DOI 10.1136/annrheumdis-2014-eular.6106

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