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Gender Specific Results in Musculo-Skeletal Research, from Bench to Bedside

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 4272

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Special Issue Editors

Dr. Manuela Salerno

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Guest Editor

Applied and Translational Research center (ATRc), IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Interests: cell biology; biotechnology; regenerative medicine; tissue engineering; women’s health

Dr. Francesca Taraballi

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Guest Editor

Center for Musculoskeletal Regeneration, Houston Methodist Academic Institute, Houston Methodist Research Institute, 6670 Bertner Ave., Houston, TX 77030, USA
Interests: biomaterials; immune-engineering; regenerative medicine; orthobiologics; translational science

Prof. Dr. Giuseppe Filardo

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Guest Editor

Applied and Translational Research center (ATRc), IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Interests: orthobiologics; musculoskeletal; osteoarthritis, cartilage; regenerative medicine

Special Issue Information

Dear Colleagues,

Male and female musculoskeletal tissues differ in several physiological features, ranging from cell molecular pathways and response to sex hormones, to anatomical and biomechanical aspects. These sex-based differences could account for the higher risk of sustaining injuries or developing degenerative conditions experienced by women, even influencing the response to therapies, the risks of adverse reactions, and treatment outcomes over time.

Thus, the importance of having clear gender-specific data on both etiopathology and treatment was underlined by the 2016 NIH request for looking at sex as a biological variable. Yet, there is alarming evidence that female sex is under-represented, and that female data are not disaggregated in preclinical and clinical studies addressing even the most common pathologies, including orthopaedic disorders. The use of preclinical in vitro and in vivo models represents the foundation of treatment development, and results based on only male subjects present a great bias and could reflect on clinical trials with serious consequences for women’s health.

Gender equity and equality should foresee the same opportunities to both sexes according to their specific needs, including the availability of adequate health service and medical treatments. To do that, it is paramount to have data that specifically document etiopathogenetic mechanisms, epidemiological distributions, as well as treatment responses in men and women. This Special Issue aims to provide data from bench to bedside on sex- and gender-specific differences in musculoskeletal disorders, and to offer women appropriate treatments that are no longer based on male data. Since IJMS is a journal of molecular science, submissions with bio-molecular experiments will be prioritized. Due to the importance of the topic and the broader scope of this Special Issue, clinical submissions with biomolecular experiments are also encouraged.

Dr. Manuela Salerno
Dr. Francesca Taraballi
Prof. Dr. Giuseppe Filardo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

sex
gender
gender bias
women's health
epidemiological gender-focused data
musculoskeletal gender-focused research
preclinical models: in vitro and in vivo
clinical gender-focused results
regenerative therapies
sex- and gender-focused reviews

Published Papers (3 papers)

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Research

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14 pages, 3193 KiB

Open AccessArticle

Retrospective Analysis of Bone Substitute Material for Traumatic Long Bone Fractures: Sex-Specific Outcomes

by Jonas Pawelke, Vithusha Vinayahalingam, Christian Heiss, Thaqif El Khassawna and Gero Knapp

Int. J. Mol. Sci. 2023, 24(18), 14232; https://doi.org/10.3390/ijms241814232 - 18 Sep 2023

Viewed by 663

Abstract

Male patients often experience increased bone and muscle loss after traumatic fractures. This study aims to compare the treatment outcomes of male and female patients with large bone defects. A total of 345 trauma patients underwent surgery, with participants divided into two groups: one receiving bone substitute material (BSM) for augmented defects (n = 192) and the other without augmentation (empty defects = ED, n = 153). Outcome parameters were assessed among female (n = 184) and male (n = 161) patients. Descriptive statistics revealed no significant differences between male and female patients. Approximately one-half of the fractures resulted from high-energy trauma (n = 187). The BSM group experienced fewer complications (p = 0.004), including pseudarthrosis (BSM: n = 1, ED: n = 7; p = 0.02). Among female patients over 65, the incidence of pseudarthrosis was lower in the BSM group (p = 0.01), while younger females showed no significant differences (p = 0.4). Radiologically, we observed premature bone healing with subsequent harmonization. Post hoc power analysis demonstrated a power of 0.99. Augmenting bone defects, especially with bone substitute material, may reduce complications, including pseudarthrosis, in female patients. Additionally, this material accelerates bone healing. Further prospective studies are necessary for confirmation. Full article

(This article belongs to the Special Issue Gender Specific Results in Musculo-Skeletal Research, from Bench to Bedside)

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16 pages, 8161 KiB

Open AccessArticle

Gender-Specific Differences in Human Vertebral Bone Marrow Clot

by Francesca Salamanna, Deyanira Contartese, Veronica Borsari, Stefania Pagani, Maria Sartori, Matilde Tschon, Cristiana Griffoni, Gianluca Giavaresi, Giuseppe Tedesco, Giovanni Barbanti Brodano, Alessandro Gasbarrini and Milena Fini

Int. J. Mol. Sci. 2023, 24(14), 11856; https://doi.org/10.3390/ijms241411856 - 24 Jul 2023

Cited by 1 | Viewed by 1025

Abstract

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials. Full article

(This article belongs to the Special Issue Gender Specific Results in Musculo-Skeletal Research, from Bench to Bedside)

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Review

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11 pages, 573 KiB

Open AccessReview

Reasons for the Sex Bias in Osteoarthritis Research: A Review of Preclinical Studies

by Madeline Franke, Chiara Mancino and Francesca Taraballi

Int. J. Mol. Sci. 2023, 24(12), 10386; https://doi.org/10.3390/ijms241210386 - 20 Jun 2023

Cited by 5 | Viewed by 1911

Abstract

Osteoarthritis (OA) is one of the most common degenerative diseases of articular cartilage. During OA, all the elements that contribute to the joint undergo physiological and structural changes that impair the joint function and cause joint pain and stiffness. OA can arise naturally, with the aging population witnessing an increase in diagnoses of this pathology, but the root causes of OA have yet to be identified, and increasing interest is arising towards investigating biological sex as a risk factor. Clinical studies show increased prevalence and worse clinical outcomes for female patients, yet most clinical and preclinical studies have disproportionately focused on male subjects. This review provides a critical overview of preclinical practices in the context of OA, highlighting the underlying need for taking biological sex as both a risk factor and an important component affecting treatment outcome. A unique insight into the possible reasons for female underrepresentation in preclinical studies is offered, including factors such as lack of specific guidelines requiring the analysis of sex as a biological variable (SABV), research-associated costs and animal handling, and wrongful application of the reduction principle. Additionally, a thorough investigation of sex-related variables is provided, stressing how each of them could add valuable information for the understanding of OA pathophysiology, as well as sex-dependent treatment strategies. Full article

(This article belongs to the Special Issue Gender Specific Results in Musculo-Skeletal Research, from Bench to Bedside)

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