Introduction

Excessive joint loadings, either single (acute contact stress caused, for example, by blunt trauma) or repetitive (cumulative contact stress caused by cyclic loading of the joint), cause progressive joint degeneration and subsequent development of the clinical syndrome of osteoarthritis (OA) [3, 4, 6, 7, 10, 13, 15, 21]. Joint injuries causing acute excessive contact stress are common and often affect young adults. Each year, one in 12 people between the ages of 18 and 44 seeks medical attention for treatment of joint injury, and more than 12% of all lower limb OA is caused by joint trauma [5]. Despite advances in surgical treatment and rehabilitation of injured joints, the risk of OA following joint fractures has not decreased in the last 50 years [3]. Recent evidence [21] shows that intraarticular fractures are accompanied by acute, rapid chondrocyte death along fracture lines in the tissue (Fig. 1). This progressive cell damage may be an effective target for therapeutic treatment to preserve cartilage metabolism and thus, reduce the risk of subsequent posttraumatic OA.

Fig. 1
figure 1

Confocal microscope images of human superficial chondrocyte viability at a representative fracture edge scan site, at the immediate, 1-day, and 2-day postfracture time points. Live cells are labeled by green fluorescence, while dead cells are labeled by red fluorescence. White arrows indicate the edge of cartilage on the fracture line. Reprinted from Tochigi Y., Buckwalter J.A., Martin J.A., Hillis S.L., Zhang P., Vaseenon T., Lehman A.D., Brown T.D.. 2011. Distribution and progression of chondrocyte damage in a whole organ model of human ankle intraarticular fracture,93(6):533–539 copyright 2011 with permission from J Bone Joint Surg Am

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Excessive Loading and Articular Cartilage Damage

Cumulative excessive contact stress at the articular surface that leads to OA can be exacerbated by joint dysplasia, incongruity, and instability [3, 4, 10, 15–18, 22], but also may cause OA in patients without known joint abnormalities [2, 20]. Advances in understanding of the thresholds for mechanical damage to articular cartilage and of the biologic mediators that cause progressive loss of articular cartilage due to excessive mechanical stress, will lead to better treatments of joint injuries and improved strategies for restoration of damaged joint surfaces [1, 3].

New Biologic and Mechanical Approaches to the Prevention and Treatment of OA

Recent in vitro investigations show that reactive oxygen species (ROS) released from mitochondria following excessive articular cartilage loading can cause chondrocyte death and matrix degradation [9, 14, 19]. Preventing the release of ROS or inhibiting their effects preserves chondrocytes and their matrix [9, 14]. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of the molecular pathways initiated by these fragments prevents this effect [8].

Distraction and motion of osteoarthritic articular surfaces can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA [11]. This result, combined with the observation that chondroprogenitor cells are active in osteoarthritic joints [12], suggests that altered loading creates an environment that promotes beneficial joint remodeling.

Summary

Taken together, these recent advances in understanding of how mechanical forces cause loss of articular cartilage including identification of mechanically induced mediators of cartilage loss and of how changing joint loading can promote joint remodeling provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA.