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Thrombospondins and Novel TSR-containing Proteins, R-spondins, Regulate Bone Formation and Remodeling

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Abstract

Thrombospondins (TSPs) are a family of five secreted multimeric matricellular proteins that share homology in the type II and III repeats and carboxy-terminal region. Type I repeats, also known as properdin or thrombospondin repeats (TSRs), are found in TSP1/2, but not TSP3-5. A variety of other secreted proteins contain TSRs, including the novel extracellular molecules, R-spondins. TSP family and many TSR-containing proteins, including R-spondins, are highly expressed in skeletal tissues during development and postnatal. TSP2 regulates the osteoblast lineage, influencing bone mass and geometry, as well as response to fracture healing, ovariectomy, and mechanical loading. Compound knockout mice of TSPs have revealed important mechanistic insights. TSP1/2 knockout mice have craniofacial dysmorphism, and TSP1/3/5 compound knockout mice display growth plate abnormalities. R-spondins promote osteoblast differentiation and R-spondin-2 deficiency results in skeletal developmental defects. Overall, TSP and other TSR molecules influence multiple aspects of bone development and remodeling.

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Disclosure

Dr. Hankenson is supported by funding from the National Institutes of Health (NIH) (R01 AR054714, R01 AR049682, and R01 DE017471), and by the NIH-funded (P30 AR050950) Penn Center for Musculoskeletal Disorders. Dr. Sweetwyne is supported by NIH grant K12-GM081259. No other potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 311 Hill Pavilion, 380 South University Avenue, Philadelphia, PA, 19104-4539, USA

    Kurt D. Hankenson, Mariya T. Sweetwyne, Hailu Shitaye & Karen L. Posey

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  1. Kurt D. Hankenson
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  2. Mariya T. Sweetwyne
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Correspondence to Kurt D. Hankenson.

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Hankenson, K.D., Sweetwyne, M.T., Shitaye, H. et al. Thrombospondins and Novel TSR-containing Proteins, R-spondins, Regulate Bone Formation and Remodeling. Curr Osteoporos Rep 8, 68–76 (2010). https://doi.org/10.1007/s11914-010-0017-0

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