Alpha 5 Integrin Mediates Osteoarthritic Changes in Mouse Knee Joints.
Osteoarthritis (OA) is one of most common skeletal disorders and can affect synovial joints such as knee and ankle joints. α5 integrin, a major fibronectin receptor, is expressed in articular cartilage and has been demonstrated to play roles in synovial joint development and in the regulation of chondrocyte survival and matrix degradation in articular cartilage. We hypothesized that α5 integrin signaling is involved in pathogenesis of OA. To test this, we generated compound mice that conditionally ablate α5 integrin in the synovial joints using the Gdf5Cre system. The compound mice were born normally and had an overall appearance similar to the control mice. However, when the mutant mice received the OA surgery, they showed stronger resistance to osteoarthritic changes than the control. Specifically the mutant knee joints presented lower levels of cartilage matrix and structure loss and synovial changes and showed stronger biomechanical properties than the control knee joints. These findings indicate that α5 integrin may not be essential for synovial joint development but play a causative role in induction of osteoarthritic changes.
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Maria Elena
ME
Candela
School of Biomedical Engineering Science, and Health Systems, Drexel University, Philadelphia, PA, United States of America.
Chao
C
Wang
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Aruni T
AT
Gunawardena
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.|Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Kairui
K
Zhang
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Leslie
L
Cantley
Division of Pathology, Department of Oral Diagnosis Science, School of Dentistry, Showa University, Tokyo, Japan.
Rika
R
Yasuhara
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Yu
Y
Usami
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Noelle
N
Francois
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Masahiro
M
Iwamoto
Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
Arjan
A
van der Flier
Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Yejia
Y
Zhang
Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.
Ling
L
Qin
School of Biomedical Engineering Science, and Health Systems, Drexel University, Philadelphia, PA, United States of America.
Lin
L
Han
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Motomi
M
Enomoto-Iwamoto
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D039482:Integrin alpha5 / Q000502:physiology*; D007719:Knee Joint / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000503:physiopathology*; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism*
D039482:Integrin alpha5