Recent Updates of Diagnosis, Pathophysiology, and Treatment on Osteoarthritis of the Knee

Abstract

Osteoarthritis (OA) is a degenerative and chronic joint disease characterized by clinical symptoms and distortion of joint tissues. It primarily damages joint cartilage, causing pain, swelling, and stiffness around the joint. It is the major cause of disability and pain. The prevalence of OA is expected to increase gradually with the aging population and increasing prevalence of obesity. Many potential therapeutic advances have been made in recent years due to the improved understanding of the underlying mechanisms, diagnosis, and management of OA. Embryonic stem cells and induced pluripotent stem cells differentiate into chondrocytes or mesenchymal stem cells (MSCs) and can be used as a source of injectable treatments in the OA joint cavity. MSCs are known to be the most studied cell therapy products in cell-based OA therapy owing to their ability to differentiate into chondrocytes and their immunomodulatory properties. They have the potential to improve cartilage recovery and ultimately restore healthy joints. However, despite currently available therapies and advances in research, unfulfilled medical needs persist for OA treatment. In this review, we focused on the contents of non-cellular and cellular therapies for OA, and briefly summarized the results of clinical trials for cell-based OA therapy to lay a solid application basis for clinical research.

Keywords: cell therapy; diagnosis; embryonic stem cells; induced pluripotent stem cells; management; mesenchymal stem cells; osteoarthritis; surgery.

Figure 1

Mechanisms for the osteoarthritis of the knee. Healthy articular cartilage (Left)—Because of absence of vessels within cartilage, chondrocytes can live in a hypoxic environment. Hypoxia is important for chondrocyte function and survival. The main function of cartilage is the absorption and the removal of mechanical load, which is necessary to maintain cartilage homeostasis. Osteoarthritis articular cartilage (Right)—Development of vessels (called vascular channels) are supposed to facilitate biochemical communication between the bone and the cartilage (such as cytokines, chemokines, alarmins). It initiates a vicious cycle of cartilage degradation.

Figure 2

The example of the Kellgren–Lawrence (KL) scale. KL classification is the most widely used radiographic scale. The radiograph was recorded at St. Mary’s Hospital in Seoul.

Figure 3

Schematic diagram of various cell-based therapy for osteoarthritis. Embryonic stem cells (ESC), induced pluripotent stem cells (iPSC), and mesenchymal stem cells (MSC) are potential candidates for cartilage regeneration for the OA treatment. MSC can be isolated from bone marrow, adipose tissue, umbilical cord, synovium. Pluripotent stem cells (PSC), including ESC and iPSC, are considered sources for the derivation of chondrocytes and MSC.