The Relationship Between Serum Relaxin and Knee Joint Laxity in Female Athletes

Arnold, Christopher; Bell, Craig Van; Rogers, Vincent; Cooney, Timothy E.

doi:10.3928/0147-7447-20020601-18

Cited by 42 publications

(10 citation statements)

References 27 publications

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“…Of the initial library screened, 82 articles were included for scoping review (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). There was overlap between analysis categories for numerous papers; most prevalent with the subjects are of cellular/molecular and systemic-musculoskeletal effects.…”

Section: Data Analysis Resultsmentioning

confidence: 99%

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Do Relaxin Levels Impact Hip Injury Incidence in Women? A Scoping Review

et al. 2022

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PurposeThe aim of this review is to assess the current evidence regarding the impact of relaxin on incidence of soft tissue hip injuries in women.MethodsA trained research librarian assisted with searches of PubMed, Embase, CINAHL, and SPORTDiscus, with a preset English language filter. The review was completed per the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis methodology. Included studies required assessment of relaxin effects on musculoskeletal health, pelvic girdle stability, or hip joint structures in human subjects. Letters, texts, and opinion papers were excluded.ResultsOur screen yielded 82 studies. Molecularly, relaxin activates matrix metalloproteinases (MMPs) including collagenases MMP-1/-13 and gelatinases MMP-2/-9 to loosen pelvic ligaments for parturition. However, relaxin receptors have also been detected in female periarticular tissues, such as the anterior cruciate ligament, which tears significantly more often during the menstrual cycle peak of relaxin. Recently, high concentrations of relaxin-activated MMP-9 receptors have been found on the acetabular labrum; their expression upregulated by estrogen.ConclusionsMenstrual cycle peaks of relaxin activate MMPs, which locally degrade collagen and gelatine. Women have relaxin receptors in multiple joints including the hip and knee, and increased relaxin correlates with increased musculoskeletal injuries. Relaxin has paracrine effects in the female pelvis on ligaments adjacent to hip structures, such as acetabular labral cells which express high levels of relaxin-targeted MMPs. Therefore, it is imperative to investigate the effect of relaxin on the hip to determine if increased levels of relaxin are associated with an increased risk of acetabular labral tears.

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Section: Data Analysis Resultsmentioning

confidence: 99%

“…Multiple factors contribute to the female predominance of ACL injuries, including neuromuscular discrepancies and fluctuating levels of reproductive hormones (7). Hormonal research has recently identified a promising target: relaxin (1,(7)(8)(9)(10). This has not been investigated in relation to young athletic hip conditions.…”

Section: Introductionmentioning

confidence: 99%

Do Relaxin Levels Impact Hip Injury Incidence in Women? A Scoping Review

et al. 2022

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“…Relaxin can lead to ligament laxity by its anti-fibrotic effects. Elevated RLN2 serum levels can increase pelvic width and height in pregnant cattle (48) , as well as tendon 29 and joint laxity (49)(50)(51) in humans. The relaxin receptor RXFP1 has been found in human female anterior cruciate ligaments (52) .…”

Section: Discussionmentioning

confidence: 99%

The anti-fibrotic effects of RLN3 aggravated the pathogenesis of adolescent idiopathic scoliosis-a preliminary study

Zhang

Luo

Sun

et al. 2022

Preprint

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Previous research proposed that ligament laxity is a clinical feature that can be easily overlooked in patients with adolescent idiopathic scoliosis (AIS). Relaxin and relaxin-related peptides, which have anti-fibrosis roles in the vascular and kidney system and relax the pubic symphysis during pregnancy, may contribute to ligament laxity. The goal of this research was to evaluate the role of in AIS. We found significantly increased relaxin-3 plasma in patients with AIS, as well as a significant correlation between joint hypermobility and relaxin 3 plasma levels. In a classic mouse model (C57BL/6J) of scoliosis, which was established according to the literature, showed significantly higher relaxin-3 plasma levels compared to normal group. In the relaxin-3 knockout C57BL/6J mice model the prevalence of scoliosis was significantly decreased. An in vitro experiment showed that relaxin 3 has anti-fibrotic effects on spinal ligament fibroblasts in both humans and mice by inhibiting TGF-β via relaxin family peptide receptor 3 (RXFP3) and increasing expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 via the TGF-β/Smad2 and MAPK-ERK1/2 pathway. Blocking RXFP3 function with R3(B1-22)R significantly decreased the prevalence of scoliosis in C57BL/6J mice. In summary, the anti-fibrotic effects of relaxin-3 and RXFP3 activation may aggravate the pathogenesis of AIS.

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“…In humans, on the other hand, relaxin has been implemented in joint disorders such as in tearing of the oblique volar ligament in the trapeziometacarpal joint [ 38 ] and in anterior cruciate ligament tears in female athletes [ 43 , 55 ]. In our cohort of dogs with CCLD, there were also more female (13) than male dogs (five), which is in accordance with known epidemiologic data in dogs: there is a 2-fold increased risk for developing cruciate ligament rupture in female dogs [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Immunoexpression of Relaxin and Its Receptors in Stifle Joints of Dogs with Cranial Cruciate Ligament Disease

Restucci

Sgadari

Fatone

et al. 2022

Animals

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The etiology of spontaneous cranial cruciate ligament rupture in dogs is unknown despite being one of the most impacting orthopedic diseases in dogs. Numerous studies have contributed to the understanding of a multifactorial pathogenesis, this, however, without identifying a pivotal link to explain progressive collagen degeneration and osteoarthritic changes. In human medicine, recent reports have identified relaxin as a triggering factor in ligament ruptures in knee and metacarpal joints. We thus hypothesized that relaxin might also play a role in canine cruciate ligament rupture. Relaxin’s primarily known property is connective tissue remodeling through collagenolysis. We therefore investigated relaxin and its cognate receptors LGR7/LGR8 in 18 dogs with cranial cruciate ligament disease (CCLD) and compared them to a group of dogs with normal stifle joints. Applying immunohistochemistry (IHC), double immunofluorescence (dIF), and western blot analysis (WB), we found strong and significantly increased expression of both relaxin and its receptors in ruptured cruciate ligaments, and in synovial membranes. Pattern of immuno-staining on dIF strongly suggests relaxin binding to primed receptors and activation of signaling properties, which in turn may have affected collagen matrix metabolism. Thus, in canine cranial cruciate ligament disease, relaxin/receptor signaling may be a primary trigger for collagen fiber degradation and collagen lysis, eventually followed by ligament rupture.

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The Relationship Between Serum Relaxin and Knee Joint Laxity in Female Athletes

Cited by 42 publications

References 27 publications

Do Relaxin Levels Impact Hip Injury Incidence in Women? A Scoping Review

Do Relaxin Levels Impact Hip Injury Incidence in Women? A Scoping Review

The anti-fibrotic effects of RLN3 aggravated the pathogenesis of adolescent idiopathic scoliosis-a preliminary study

Immunoexpression of Relaxin and Its Receptors in Stifle Joints of Dogs with Cranial Cruciate Ligament Disease

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