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    ASBMR 31st Annual Meeting

    Intermittent PTH(1-34) and PTHrP Enhance Hyaline Cartilage Regeneration in a Rabbit Full-Thickness Defect Model

    Category: Bone, Cartilage and Connective Tissue Matrix & Development (Basic)

    Poster Sessions, Presentation Number: SU0070
    Session: Poster Session II
    Sunday, September 13, 2009 12:00 AM - 12:00 AM, Colorado Convention Center, Exhibit Hall F

    * Erik Sampson, University of Rochester, USA, Hsin Chiu Ho, University of Rochester, USA, Hani Awad, Department of Biomedical Engineering, USA, Susan Bukata, UCLA, USA, J. Edward Puzas, University of Rochester School of Medicine, USA, Regis O'Keefe, University of Rochester, USA, Michael Zuscik, University of Rochester School of Medicine & Dentistry, USA, Randy Rosier, University of Rochester Medical Center, USA

    The limited regenerative capacity of articular cartilage is a significant obstacle in the treatment of cartilage defects and preventing the development of osteoarthritis (OA). OA is a degenerative joint disease projected to afflict 59.4 million Americans (18%) by 2020. There are a variety of surgical procedures used to repair articular cartilage defects, including drilling, microfracture, mosaicplasty, allografts, and autologous chondrocyte transplantation. Bone marrow-stimulating procedures, such as drilling and microfracture, penetrate subchondral bone underlying the articular cartilage defect to induce repair tissue formation. However, the resulting cartilage is typically either a mixture of hyaline and fibrocartilage or predominantly fibrocartilage. It follows that stimulating the proliferation and inhibiting the maturation of chondro-progenitor cells recruited to the repair tissue may enhance hyaline cartilage regeneration. Given the well-established role of Parathyroid Hormone (PTH)-related Protein (PTHrP) in restricting hypertrophy and inducing proliferation in the developing growth plate, we hypothesized that this factor or the related molecule, PTH, would enhance hyaline cartilage regeneration in a rabbit full-thickness defect model. To test this hypothesis, we created 3mm full-thickness articular cartilage defects in the medial femoral condyles of New Zealand White rabbits. Sham surgery was performed on the contralateral condyles. Rabbits then began daily, systemic treatment with saline, or 10μg/kg Forteo®/teriparatide (Eli Lilly formulation of PTH1-34), PTH(1-34) (teriparatide, Sigma) or PTHrP(1-34) (Sigma). Rabbits were subsequently sacrificed at 4, 8, and 12 weeks following surgery and condyles were harvested for histologic analysis. Although there was evidence of hyaline cartilage regeneration in saline-treated animals at 4 weeks post-surgery, there was primarily fibrocartilage at 8 and 12 weeks, perhaps reflecting chondrocyte maturation or loss of chondrogenic potential with time. In contrast, animals treated with teriparatide or PTHrP had highly variable hyaline cartilage regeneration at 4 weeks with progressively enhanced regeneration at 8 and 12 weeks compared to saline treatment. These data demonstrate that the propensity for fibrocartilage formation in full-thickness defect repair tissue can be altered by intermittent teriparatide or PTHrP treatment, enhancing hyaline regeneration and potentially inhibiting OA development.

    Disclosures: None

    * Presenting Authors(s): Erik Sampson, University of Rochester, USA