What’s New in Orthopaedic Research

Abstract

Exciting advances continue to be made in numerous areas of orthopaedic research. One of the most important areas of research continues to be the discovery of biologic solutions to degenerative joint disease. Emerging information about the genetic basis of bone and cartilage pathology is being used to provide insight into the fundamental mechanisms of common conditions such as osteoporosis, degenerative disc disease, and arthritis. Other active areas of investigation include stem cells, growth factors, tissue engineering, biomaterials, and the biomechanical properties of tissues at the nanoscale. Another common theme is improving the understanding of the basic cellular mechanisms that control the response of musculoskeletal tissues to mechanical load. Investigations in these areas have the potential to improve current treatments and to lead to the development of novel therapies and implants. This paper reviews several major areas of active investigation. ### Bone and Skeletal Development A study of mice deficient in membrane-type 1 matrix metalloproteinase (MT1-MMP) showed that MT1-MMP plays a fundamental role in a novel mechanism of remodeling of unmineralized cartilage anlagen into membranous bone, ligament, and tendon1. While the most common mechanisms of remodeling in the skeleton (endochondral ossification and postnatal bone remodeling) involve replacement of a mineralized matrix by a newer mineralized matrix, in this newly discovered process MT1-MMP directs dissolution of unmineralized cartilage and apoptosis of nonhypertrophic chondrocytes. This process occurs without progression through the sequence of matrix mineralization. MT1-MMP also allows remodeling of cartilage into ligament at insertion sites. MT1-MMP is expressed at ligament insertion sites, implying that this molecule likely plays an important role in soft tissue-bone attachment. Human genetic diseases can provide a mechanism for identifying genes that are important for bone formation. Genetic studies also may shed light on the sensitivity of bone to mechanical loading. It is known that some individuals respond better to exercise …