Skeletal Development and Regeneration Research: Jennifer J. Westendorf

Protein Phosphatase Phlpp1 in Cartilage Development and Osteoarthritis Progression

Dr. Westendorf's Skeletal Development and Regeneration Research Laboratory is studying protein phosphatase Phlpp1 in cartilage development and osteoarthritis progression.

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Articular cartilage

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Articular cartilage on the medial side of a mouse knee joint. The femur (top), tibia (bottom) and meniscus (left) are shown. Bone is blue-green, cartilage is pink and cells and bone marrow are pink-purple. Credit: Soyun Michelle Hwang.

Related publications

• Mattson AM, Begun DL, Molstad DHH, Meyer MA, Oursler MJ, Westendorf JJ, Bradley EW. Deficiency in the phosphatase PHLPP1 suppresses osteoclast-mediated bone resorption and enhances bone formation in mice. Journal of Biological Chemistry. 2019; doi:10.1074/jbc.RA119.007660.
• Zhang C, Smith MP, Zhou GK, Lai A, Hoy RC, Mroz V, Torre OM, Laudier DM, Bradley EW, Westendorf JJ, Latridis JC, Illien-Junger S. Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice. Cell Death and Disease. 2019; doi:10.1038/s41419-019-1985-3.
• Castillejo Becerra CM, Mattson AM, Molstad DHH, Lorang IM, Westendorf JJ, Bradley EW. DNA methylation and FoxO3a regulate PHLPP1 expression in chondrocytes. Journal of Cellular Biochemistry. 2018; doi:10.1002/jcb.27056.
• Hwang SM, Feigenson M, Begun DL, Carpio Shull LR, Culley KL, Otero M, Goldring MB, Ta LE, Kakar S, Bradley EW, JJ Westendorf JJ. Phlpp inhibitors block pain and cartilage degradation associated with osteoarthritis. Journal of Orthopaedic Research. 2018; doi:10.1002/jor.23781.
• Bradley EW, Carpio LR, McGee-Lawrence ME, Castillejo Becerra C, Amanatullah DF, Ta LE, Otero M, Goldring MB, Kakar S, Westendorf JJ. Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis. Osteoarthritis and Cartilage. 2016; doi:10.1016/j.joca.2015.12.014.
• Bradley EW, Carpio LR, Newton AC, Westendorf JJ. Deletion of the PH-domain and leucine-rich repeat protein phosphatase 1 (Phlpp1) increases fibroblast growth factor (Fgf) 18 expression and promotes chondrocyte proliferation. Journal of Biological Chemistry. 2015; doi:10.1074/jbc.M114.612937.
• Bradley EW, Carpio LR, Westendorf JJ. Histone deacetylase 3 suppression increases PH domain and leucine-rich repeat phosphatase (Phlpp)1 expression in chondrocytes to suppress Akt signaling and matrix secretion. Journal of Biological Chemistry. 2013; doi:10.1074/jbc.M112.423723.