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bioRxiv · 10.1101/715102

The impact of genistein supplementation on tendon functional properties and gene expression in estrogen deficient rats

Carroll, C.·Patel, S. H.·Simmons, J.·Gordon, B. D.·Olson, J. F.·Chemelewski, K.·Saw, S.·Hale, T. M.·Howden, R.·Sabbaghi, A.
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Abstract

PurposeTendinopathy risk increases with menopause. The phytoestrogen genistein prevents collagen loss during estrogen deficiency [ovariectomy (OVX)]. The influence of genistein on tendon function and extracellular matrix (ECM) regulation are not well known. We determined the impact of genistein on tendon function and examined potential mechanisms by which genistein alters tendon ECM.\n\nMaterials and MethodsEight-week-old rats (n=42) were divided into three groups: intact, OVX, or OVX-genistein (6mg/kg/day) for 6-weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet PCR. Tendon-derived fibroblasts were also treated with genistein in the presence of estrogen receptor (ER) antagonists.\n\nResultsCompared to intact, stress tended to be lower in untreated OVX rats (p=0.022). Further, modulus and energy density were greater in genistein-treated rats (p<0.05) compared to intact. Neither OVX nor genistein altered expression of Col1a1, Col3a1, Casp3, Casp8, Mmp1a, Mmp2, or Mmp9 (p>0.05). Compared to intact, Tnmd and Esr1 expression was greater and Pcna and Timp1 expression lower in OVX rats (p<0.05). Genistein treatment returned Tnmd, Pcna, and Timp1 to levels of Intact-Vehicle (p<0.05), but did not alter Scx or Esr1 (p>0.05). Several {beta}-catenin/Wnt signaling related molecules were not altered by OVX or genistein (p>0.05). In vitro, genistein blunted cell proliferation but not via ERs.\n\nConclusionsOur findings demonstrate that genistein improves tendon function. Genistein inhibits cell proliferation in vitro but not via ER. The effect of genistein in vivo was predominately on genes related to cell proliferation rather than collagen remodeling.

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Carroll, C., Patel, S. H., Simmons, J., Gordon, B. D., Olson, J. F., Chemelewski, K., Saw, S., Hale, T. M., Howden, R., Sabbaghi, A.. 2019-07-26. The impact of genistein supplementation on tendon functional properties and gene expression in estrogen deficient rats. https://doi.org/10.1101/715102

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