Differential effects of Epigallocatechin-3-gallate containing supplements on correcting skeletal defects in a Down syndrome mouse model

• Published in: Molecular nutrition & food research 2016-04, Vol.60 (4), p.717-726
• Main Authors: Abeysekera, Irushi, Thomas, Jared, Georgiadis, Taxiarchis M., Berman, Alycia G., Hammond, Max A., Dria, Karl J., Wallace, Joseph M., Roper, Randall J.
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Animals; Bone and Bones - abnormalities; Bone and Bones - drug effects; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Dietary Supplements; Disease Models, Animal; Down syndrome; Down Syndrome - diet therapy; Down Syndrome - physiopathology; Epigallocatechin-3-gallate; Female; Femur - diagnostic imaging; Femur - drug effects; Femur - physiopathology; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Mouse model; Skeletal deficits; Supplements; X-Ray Microtomography
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500781

Scope Down syndrome (DS), caused by trisomy of human chromosome 21 (Hsa21), is characterized by a spectrum of phenotypes including skeletal abnormalities. The Ts65Dn DS mouse model exhibits similar skeletal phenotypes as humans with DS. DYRK1A, a kinase encoded on Hsa21, has been linked to deficiencies in bone homeostasis in DS mice and individuals with DS. Treatment with Epigallocatechin‐3‐gallate (EGCG), a known inhibitor of Dyrk1a, improves some skeletal abnormalities associated with DS in mice. EGCG supplements are widely available but the effectiveness of different EGCG‐containing supplements has not been well studied. Methods and results Six commercially available supplements containing EGCG were analyzed, and two of these supplements were compared with pure EGCG for their impact on skeletal deficits in a DS mouse model. The results demonstrate differential effects of commercial supplements on correcting skeletal abnormalities in Ts65Dn mice. Different EGCG‐containing supplements display differences in degradation, polyphenol content, and effects on trisomic bone. Conclusion This work suggests that the dose of EGCG and composition of EGCG‐containing supplements may be important in correcting skeletal deficits associated with DS. Careful analyses of these parameters may lead to a better understanding of how to improve skeletal and other deficits that impair individuals with DS. Epigallocatechin‐3‐gallate (EGCG) is a potential therapeutic for Down syndrome (DS) phenotypes. Though many EGCG‐containing supplements are available, they differ in content of EGCG as well as other polyphenols. Different EGCG‐containing supplements vary in their effects on skeletal deficiencies associated with DS in mouse models. Though some EGCG containing supplements improve the skeletal microarchitecture (Tb.Th) of Ts65Dn DS as compared to euploid mice, they also decrease the stiffness of the bone. Further testing should be done on how EGCG‐containing supplements may affect other DS phenotypes.