Relaxin and insulin‐like peptide 3 in the musculoskeletal system: from bench to bedside

Ferlin, Alberto; Toni, Luca De; Sandri, Marco; Foresta, Carlo

doi:10.1111/bph.13490

Cited by 27 publications

(24 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding is consistent with a previous report that relaxin may stimulate osteoblast activity, resulting in bone formation (Ferlin et al. ). The results support the possibility that, perhaps in contrast to the calvaria, femur vasculature, osteoblasts and/or osteoclasts may express RXFP1 receptors, thus leading to enhanced trabecular growth by relaxin.…”

Section: Discussionsupporting

confidence: 94%

“…A somewhat incidental finding was that relaxin may have stimulated trabecular bone growth in an uninjured bone (femur) as evidenced by higher Tb.Th and lower Tb.Pf (Table 5). This finding is consistent with a previous report that relaxin may stimulate osteoblast activity, resulting in bone formation (Ferlin et al 2017). The results support the possibility that, perhaps in contrast to the calvaria, femur vasculature, osteoblasts and/or osteoclasts may express RXFP1 receptors, thus leading to enhanced trabecular growth by relaxin.…”

Section: Discussionsupporting

confidence: 93%

“…; Ferlin et al. ). Moreover, relaxin has a good safely record based on human clinical trials for other indications (Said and Mukherjee ; Ghosh et al.…”

Section: Discussionmentioning

confidence: 98%

“…Hence, therapeutic agents that will improve bone perfusion may accelerate healing of fracture lesions. To this end, we reasoned that relaxin may potentially be a therapeutic molecule, because the hormone possesses biological attributes that theoretically speaking could improve (1) local angiogenesis, (2) vasculogenesis and osteogenesis by mobilizing and activating BMPC, (3) blood flow via vasodilation, (4) bone formation by directly acting on osteoblasts and/or osteoclasts, and reduce (5) inflammation (Masini et al 2004;Jeyabalan et al 2007;Conrad 2010Conrad , 2011Brecht et al 2011;Segal et al 2012;Ferlin et al 2017). Moreover, relaxin has a good safely record based on human clinical trials for other indications (Said and Mukherjee 2013;Ghosh et al 2017).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

et al. 2019

View full text Add to dashboard Cite

Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

“…; Ferlin et al. ). Moreover, relaxin has a good safely record based on human clinical trials for other indications (Said and Mukherjee ; Ghosh et al.…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…For example, INSL3, the testisspecific protein hormone secreted by Leydig cells, may act on bone by inducing the expression of some key osteoblast genes for osteoblast differentiation, matrix deposition, and osteoclastogenesis. It may also act by stimulation of mineralization and/or promoting better function of the muscle-skeletal unit [Ferlin et al, 2016]. Even though the INSL3 status of women with CAIS who maintained their gonads is unknown, this hormone is obviously absent in those females who underwent gonadal removal.…”

Section: Causes Of Impaired Bmd In Women Living With Caismentioning

confidence: 99%

Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads

Bertelloni

Meriggiola²,

Dati

et al. 2017

Sex Dev

View full text Add to dashboard Cite

Complete androgen insensitivity syndrome (CAIS) is due to complete androgen resistance in androgen-dependent tissues. Since androgens are involved in growth, development, and mass maintenance of the skeleton, bone health may be a relevant clinical issue for improving quality of life of women living with CAIS. Bone mineral density (BMD) in women with CAIS and intact gonads has been reported in a normal range, although exceptions are known showing a low BMD mainly at the lumbar level. In women with CAIS and removed gonads, BMD is usually reduced at both the lumbar spine and femoral neck. However, the fracture risk remains largely unknown. In women with CAIS, hormonal replacement therapy may improve BMD, but it does not normalize it. Several factors may be operative (e.g., loss of AR signaling at the bone level, gonadal removal, and age at surgery [before or after attainment of the peak bone mass], inadequate sex steroid replacement therapy, poor compliance with hormonal treatment, high serum FSH levels, lack of testicular protein hormones after gonadal removal), but they are poorly evaluated. In conclusion, the maintenance of testes may represent a strategy to improve bone health in women with CAIS, but a strict follow-up to monitor the cancer risk is mandatory mainly from their 20s onwards. Optimal sex steroid substitutive therapy in adolescence and adulthood is a key factor to improve BMD status in women with CAIS and removed gonads, but conclusive data on optimal management are lacking.

show abstract

Testicular Function and Skeletal Alterations

Ferlin

2020

Trends in Andrology and Sexual Medicine

View full text Add to dashboard Cite

Relaxin and insulin‐like peptide 3 in the musculoskeletal system: from bench to bedside

Abstract: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.

Cited by 27 publications

References 88 publications

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

Potential therapeutic use of relaxin in accelerating closure of cranial bone defects in mice

Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads

Testicular Function and Skeletal Alterations

Contact Info

Product

Resources

About