The Impact of Genistein Supplementation on Tendon Functional Properties and Gene Expression in Estrogen-Deficient Rats

Tendinopathy 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 is not well known. We determined the impact of genistein on tendon function and the expression of several genes important for the regulation of tendon ECM. Eight-week-old rats (n = 42) were divided into three groups: intact, OVX, or OVX-genistein (6 mg/kg/day) for 6 weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet polymerase chain reaction. Compared to intact, fascicle stress tended to be lower in untreated OVX rats (P = .022). Furthermore, fascicle modulus and energy density were greater in genistein-treated rats (P < .05) compared to intact. Neither OVX nor genistein altered expression of Col1a1, Col3a1, Casp3, Casp8, Mmp1a, Mmp2, or Mmp9 (P > .05). Compared to intact, Tnmd and Esr1 expression were greater and Pcna and Timp1 expression were lower in OVX rats (P < .05). Genistein treatment returned Tnmd, Pcna, and Timp1 to levels of intact-vehicle (P < .05), but did not alter Scx or Esr1 (P > .05). Several beta-catenin/Wnt signaling-related molecules were not altered by OVX or genistein (P > .05). Our findings demonstrate that genistein improves tendon function in estrogen-deficient rats. The effect of genistein in vivo was predominately on genes related to cell proliferation rather than collagen remodeling.