Photodynamic treatment has chondroprotective effects on articular cartilage

Journal of Orthopaedic Research - Tập 20 - Trang 241-248 - 2002
Lawrence G Sullivan1, Tayyaba Hasan2, Marianne Wright1, Henry J Mankin1, Christine A Towle1
1Department of Orthopaedic Surgery, Harvard Medical School, Orthopaedic Research Laboratories, Massachusetts General Hospital, GRJ 1124, 55 Fruit Street, Boston, MA 02114, USA
2Department of Pathology, Harvard Medical School, Wellman Laboratories of Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA

Tóm tắt

Abstract

Osteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor‐β, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin‐1 (IL‐1). The problems associated with selective delivery of the growth factor to chondrocytes, undesirable side‐effects on joint tissues, and short biological half‐life have led us to explore modalities aimed at activating transforming growth factor‐β that is stored in the cartilage as latent complexes. Photodynamic therapy is a two‐step protocol of tissue sensitization with a light‐activatable chemical called a photosensitizer followed at some interval by irradiation with the appropriate wavelength visible light. Biological effects are typically elicited through oxygen‐dependent photochemistry without heat generation. Transforming growth factor‐β1 can be activated by oxidative mechanism(s), prompting us to explore whether photodynamic technology can be harnessed to modulate cartilage metabolism. Disks of bovine articular cartilage were photosensitized by incubation with a chlorine6‐succinylated polylysine conjugate and irradiated with 1–2 J/cm2 red light (λmax = 671 nm). This two‐step regimen dramatically inhibited IL‐1‐stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor‐β1 in culture medium. This research may lead to the development of minimally invasive photodynamic therapy in which light is delivered to locally activate a chondroprotective program in photosensitized cartilage in the context of OA. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.


Tài liệu tham khảo

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Journal of Orthopaedic Research

Tập 20

241-248

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