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THE EFFECT OF GENDER ON THE MOLECULAR PROFILE OF TENDON HEALING FROM LACERATION
Presenter: Peter J Taub, MD, FACS, FAAP
Co-Authors: George N; Flatow EL; Andarawis-Puri N
Mount Sinai Medical Center

Introduction: Females suffer a higher incidence of tendon injuries than males[1]. Studies have shown that female tendons exhibit lower collagen and glycosaminoglycan content than male tendons[2] and poorer adaptation to exercise (with lower up-regulation of collagens)[2]. However, the effect of gender on the molecular healing response of lacerated tendons has not been fully characterized. The objective was to identify differences in 84 genes involved in fibrotic wound healing between genders after tendon laceration.

Methods: A defect in the patellar tendon of 16 week-old male (n=6) and female (n=6) mice was created with a punch biopsy. The tendon was harvested 1 week after injury. RNA was extracted, cDNA synthesized and qPCR for 84 genes was performed using SyBr green. ?CT values were calculated relative to nave control and then linearized. Comparisons between groups were determined with Mann Whitney tests. Significance was set at p<0.05.

Results: Male tendons exhibited a response that suggests better healing than female tendons. Compared to their respective nave groups, experimental male and female tendons exhibited up-regulation in MMP-2, -3, and -14. Experimental males also exhibited further up-regulation of MMP-13 than both, nave males and experimental females (p=.0022). Genes that activate (Smad2, Tfb1 and Tgif1) and inhibit (Smad6, Grem1) TGF≤≤ pathways were significantly different between experimental groups. All p-values were 0.0022 except for Grem1, which had a p=.0422.

Discussion: The 19 genes that differed in males and females provide insight into gender and wound healing, and support our hypothesis that male tendons modulate gene expression differently to promote better healing. MMP-13, which is integral to degradation of damaged matrix[6], was significantly more upregulated in experimental males than females. Consistent with findings showing regulation of MMP13 by Il1b[7], we also found up-regulation of Il1b in male but not female tendons. Male tendons exhibited further upregulation of more transcription and growth factors than females, suggesting improved healing with better vascularization.


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