Serum and Synovium Protease Inhibitor Levels in Primary and Secondary Osteoarthritic Joints

Summary

Osteoarthritis (OA) is the irreversible degeneration of articular cartilage and underlying bone. It poses a major healthcare problem as it is the leading cause of joint disease and disability in the United States. It was traditionally thought that OA was a consequence of aging and joint trauma. However, it is now thought that OA is a result of the interplay of multiple genetic, biomechanical, and biochemical factors that disrupt the normal homeostasis of cartilage, bone, and synovium.

OA is classified into two groups, primary and secondary. Primary OA is classically polyarticular and peripheral while secondary OA can commonly be attributed to a specific cause, limited to a singular joint, and a result of trauma. It is known as post-traumatic OA (PTOA). Other causes of secondary OA include congenital disorders, calcium pyrophosphate dehydrate deposition disease, and other diseases. Regardless of classification, genetic variation in the normal metabolism of cartilage and bone is thought to play a role in the progression of OA. Furthermore, the polyarticular presentation of primary idiopathic osteoarthritis suggests that it may have a stronger genetic component as compared to secondary OA, indicating a deviation from normal cartilage and bone homeostasis.

Matrix metalloproteinases (MMP) and their inhibitors take part in the metabolism of cartilage and bone. MMPs are enzymes that catalyze the degradation of elements within joint spaces while their inhibitors cease this activity. Alpha-2-Macroglobulin (A2M) is a naturally-occurring plasma glycoprotein that functions throughout multiple tissues and extracellular spaces as a protease inhibitor but does not normally reach high levels within the intra-articular joint space. A2M is believed to modulate the systemic inflammatory response by its ability to bait, trap, and clear various MMPs and cytokines. Concentrated A2M directly addresses the roles of cytokines and catabolic enzymes known to participate in the development of osteoarthritis. Cytonics has shown that A2M can inhibit cartilage degradation in vitro. As the role of MMPs and protease inhibitors have emerged as key components of OA, the investigation of regulators of MMP has become of interest to elucidate the pathogenesis and possible novel treatments of OA.

This study aims to measure and correlate the levels of alpha-2-Macroglobulin (A2M) in plasma and knee joint OA between primary post-traumatic (PTOA) and secondary osteoarthritis groups.

Conditions

• Osteoarthritis of the Knee

Interventions

PROCEDURE

Blood Draw

Blood drawn for A2M levels to be assayed at Cytonics

PROCEDURE

Joint Aspirate Harvest

Joint aspirate harvested for A2M levels to be assayed at Cytonics

PROCEDURE

Blood Draw

Blood drawn for A2M levels to be assayed at Cytonics

PROCEDURE

Joint Aspirate Harvest

Joint aspirate harvested for A2M levels to be assayed at Cytonics

Sponsors & Collaborators

• Scuderi, Gaetano J., M.D.

  lead OTHER

Principal Investigators

• Gaetano Scuderi, MD · Stanford University, Dept. of Orthopedic Surgery

Eligibility

Min Age

19 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-03-31

Primary Completion

2018-08-31

Completion

2018-08-31

Countries

• United States

Study Locations