title: Photodynamic treatment has chondroprotective effects on articular cartilage.
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-beta, 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-beta 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-beta1 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 chlorin(e6)-succinylated polylysine conjugate and irradiated with 1-2 J/cm2 red light (lambdamax = 671 nm). This two-step regimen dramatically inhibited IL-1-stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor-beta1 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.
authors.affiliation: Department of Orthopaedic Surgery, Harvard Medical School, Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Sullivan
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.forename: Marianne
authors.initials: M
authors.lastname: Wright
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mankin
authors.forename: Christine A
authors.initials: CA
authors.lastname: Towle
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D002417:Cattle; D002735:Chlorophyllides; D006025:Glycosaminoglycans / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D010778:Photochemotherapy; D011107:Polylysine / Q000737:chemistry; D011166:Porphyrins / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
chemical_list: D002735:Chlorophyllides; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D011107:Polylysine; C062985:phytochlorin