Does estrogen alter the mechanical properties of the anterior cruciate ligament?: An experimental study in rabbits

Komatsuda, Tatsuro; Sugita, Takehiko; Sano, Hirotaka; Kusakabe, Takashi; Watanuki, Munenori; Yoshizumi, Yusuke; Murakami, Takashi; Hashimoto, Minoru; Kokubun, S.

doi:10.1080/17453670610013312

Cited by 35 publications

(23 citation statements)

References 23 publications

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“…In a rat osteoporosis model created by an ovariectomy, Yoshida et al subcutaneously injected estradiol into the experimental group and found that the ACL is ER-dependent and that estrogen may alter ligament tissue composition, especially in the proximal position (15). The amount of estrogen used in our study is based on the articles previously conducted using subcutaneous estrogen in rats and rabbits, and we adjusted the dosage via transformation formula considering the species, route of medication and body surface area (15,32). The amount of estrogen used in our study is based on the articles previously conducted using subcutaneous estrogen in rats and rabbits, and we adjusted the dosage via transformation formula considering the species, route of medication and body surface area (15,32).…”

Section: Discussionmentioning

confidence: 99%

Use of Estradiol Promotes Graft‐Bone Healing in Rabbit Model of Anterior Cruciate Ligament Reconstruction With a Polyethylene Terephthalate Ligament

et al. 2017

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The purpose of this study was to investigate whether the local use of estradiol after anterior cruciate ligament (ACL) reconstruction with a polyethylene terephthalate (PET) artificial ligament graft could promote graft-bone healing. A total of 45 New Zealand white rabbits underwent ACL reconstruction with a PET ligament graft. The experimental groups were administered a local estradiol injection at either a low dose after surgery or a high dose after surgery, and the control group did not receive an injection. Computed tomography (CT) scans and blood sample collection were routinely performed in all three groups. Over time, the serum estradiol levels increased in both experimental groups, and the CT images revealed a trend of a shrinking bone tunnel area in all three groups. The rabbits were randomly sacrificed at 2, 4, and 8 weeks after surgery. The load to failure and stiffness of the experimental groups were significantly higher than those of the control group at 4 and 8 weeks. The histological study identified more bone mineralization in the experimental groups at 4 weeks after surgery compared to the control group. This study showed that the use of estradiol is a promising approach in promoting graft-bone healing in rabbits undergoing ACL reconstruction with a PET ligament graft.

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Section: Discussionmentioning

confidence: 99%

Use of Estradiol Promotes Graft‐Bone Healing in Rabbit Model of Anterior Cruciate Ligament Reconstruction With a Polyethylene Terephthalate Ligament

et al. 2017

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“…Various factors, including skeletal maturity, aging, daily activity, exercise, sex, and hormonal factors, influence the properties of these tissues [13,14]. It is not known if estrogen affects tendons and ligaments [15][16][17]. Previous studies, however, indicate the presence of estrogen receptors (ER) in tendons and ligaments [18,19].…”

Section: Introductionmentioning

confidence: 96%

Effect of Selective Estrogen Receptor Modulator/Raloxifene Analogue on Proliferation and Collagen Metabolism of Tendon Fibroblast

Irie

Takahata

Majima

et al. 2010

Connective Tissue Research

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The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17beta-Estradiol (E(2); 10(-11)-10(-9) M) and LY117018 (10(-9)-10(-7) M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2'-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E(2) nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E(2) and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E(2) and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E(2) or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels.

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“…11,41 Because differences in ligament size may play a role in the strength of knee ligaments, several methods, including computer modeling, 11 measurement from magnetic resonance imaging, 41 and micrometers, 42 have been used to account for various ligament sizes when calculating tensile and mechanical properties. Although these methods have routinely been used on larger human ligaments, the small size and structure of the rat ACL makes similar methods difficult to employ.…”

Section: Discussionmentioning

confidence: 99%

Sex, Collagen Expression, and Anterior Cruciate Ligament Strength in Rats

Romani

Langenberg

Belkoff

2010

Journal of Athletic Training

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Context: Sex-specific responses to steroid sex hormones have been suggested as a potential cause for the disparate anterior cruciate ligament (ACL) injury rates between male and female athletes. Type 1 collagen (T1C) and type 3 collagen (T3C) are crucial structural components that define the ligament's ability to withstand tensile loads. Messenger RNA (mRNA) is an important mediator of downstream collagen synthesis and remodeling, but the sex-specific mechanisms of collagen mRNA expression and ACL strength are unknown.Objective: To examine the influence of sex on T1C and T3C mRNA expression and mass-normalized stiffness and peak failure load in the ACLs of skeletally mature rats.Design: Observational study. Setting: Basic sciences and biomechanical testing laboratories.Patients or Other Participants: Nineteen 12-week-old male (n 5 9) and female (n 5 10) Sprague Dawley rats.Main Outcome Measure(s): We used real-time polymerase chain reaction to determine T1C and T3C mRNA expression and a hydraulic materials testing device to measure ACL stiffness and failure load. Nonparametric Wilcoxon rank sum tests were used to compare the groups.Results: Female rats had lower amounts of T3C mRNA expression and higher normalized ACL tangent stiffness and failure load than male rats.Conclusions: These findings suggest that sex-specific differences in T1C and T3C mRNA expression may play an important role in the downstream mechanical properties of the ACL.Key Words: knee injuries, women's health, real-time polymerase chain reaction Key Points N Compared with male rats, female rats demonstrated less type 3 collagen messenger RNA (mRNA) expression and greater normalized anterior cruciate ligament stiffness and load to failure.N Sex-specific differences in type 1 and type 3 collagen mRNA expression may influence the mechanical properties of the anterior cruciate ligament.T he anterior cruciate ligament (ACL) provides as much as 86% of the passive anterior restraint of the tibia on the femur. 1 As a result, ACL injuries often require surgical reconstruction and extensive rehabilitation to restore knee stability and ensure a full functional recovery. The long-term consequences of ACL injuries include accelerated knee joint degeneration; laxity; osteophyte formation; and type 2 collagen degradation, which may lead to early onset of osteoarthritis. [2][3][4][5] Most ACL injuries result from high tensile loads applied to the ligament during sudden changes of direction and jumping. 6 Whereas sex differences in landing and running biomechanics may place the ACL at risk, 7,8 the structure's ability to withstand those tensile loads likely depends upon several factors, including ligament size, rate of collagen remodeling, and collagen isoform. 9-11 Type 1 collagen (T1C) accounts for up to 87% 9,12 of the ligament's collagen content 9,12-14 and, along with type 3 collagen (T3C), acts to resist the loads applied to the ACL. 9,12 Type 3 collagen is also believed to play an important role in healing. [13][14][15] The extracellular matrix (ECM), ...

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Does estrogen alter the mechanical properties of the anterior cruciate ligament?: An experimental study in rabbits

Abstract: Our findings suggest that high SEL might be one of the factors in the multifactorial pathogenesis of ACL rupture.

Cited by 35 publications

References 23 publications

Use of Estradiol Promotes Graft‐Bone Healing in Rabbit Model of Anterior Cruciate Ligament Reconstruction With a Polyethylene Terephthalate Ligament

Use of Estradiol Promotes Graft‐Bone Healing in Rabbit Model of Anterior Cruciate Ligament Reconstruction With a Polyethylene Terephthalate Ligament

Effect of Selective Estrogen Receptor Modulator/Raloxifene Analogue on Proliferation and Collagen Metabolism of Tendon Fibroblast

Sex, Collagen Expression, and Anterior Cruciate Ligament Strength in Rats

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