A Study of Enthesopathy in X-Linked Hypophosphatemia

Program Faculty & Summary

Carolyn Macica, PhD

Carolyn Macica’s study focused on a particularly debilitating complication of XLH, enthesopathy. She studied the progression and pathogenesis of the calcification of tendon and ligament insertion sites.

Dr. Macica states: "The formation of enthesophytes was our focus, with a major emphasis on characterizing the cellular changes that occur in enthesophyte formation using the murine model of XLH, Hyp mice. We have found that mineralization, while thought to originate from bone, is actually due to both an expansion of fibrocartilage cells that express the FGFR3 receptor and an increase in alkaline phosphatase activity.

We investigated the role of elevated circulating levels of FGF23 in fibrocartilage expansion using FGFR2 knockout mice on the Hyp background and in Dmp1 knockout mice, another model of osteomalacia characterized by elevated FGF23 levels, independent of the Phex mutation. We have evidence that an increase in chondrocyte-derived alkaline phosphatase is likely involved in the mineralization of both entheses and articular cartilage. We also sought to better characterize the dysregulation of alkaline phosphatase specific to cells of chondrocyte (vs. osteoblast) origin."

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