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Musculoskeletal Biology: Impact of Ageing and Disease
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Musculoskeletal Biology: Impact of Ageing and Disease

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Physiology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 14368

Special Issue Editors

Dr. Rachel A. Oldershaw

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Guest Editor
MRC-Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Ageing, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L7 8TX, UK
Interests: musculoskeletal system; joint; chronic disease; frailty; ageing
Prof. Dr. Anne McArdle

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Guest Editor
MRC-Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal Ageing, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L7 8TX, UK
Interests: skeletal muscle ageing; musculoskeletal system; nutrition and frailty; cell models; human interventions

Special Issue Information

Dear Colleagues, 

The prevalence of disorders associated with the musculoskeletal system continues to increase with the ageing population, resulting in escalating societal and economic burdens placed on healthcare systems.

There is, therefore, a critical need to strengthen our understanding of the biological changes that take place in the musculoskeletal system during the process of normal ageing and at the onset and progression of diseases that affect skeletal muscle, bone, cartilage, joints, tendons and ligaments.

This research topic aims to address unsolved problems in the field of musculoskeletal and ageing science at the molecular, cellular, tissue, organ and systems levels, and will seek to advance new ways of understanding, diagnosing, treating and preventing ageing and chronic diseases of the musculoskeletal system.

This Special Issue welcomes original research articles, reviews, methods, and other article types focused on (but not limited to) the following areas:

  • Mechanisms and models of ageing and musculoskeletal disease;
  • Biology of musculoskeletal tissues (including skeletal muscle, bone, cartilage, joints, tendons and ligaments);
  • Biomechanics;
  • Nutrition and frailty;
  • Pain.

We look forward to receiving your contributions.

Dr. Rachel A. Oldershaw
Prof. Dr. Anne McArdle
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. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • musculoskeletal system
  • joint
  • chronic disease
  • frailty
  • ageing

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Published Papers (7 papers)

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14 pages, 2607 KiB  
Article
Mandibular-Derived Monocytes from 1-Year-Old Mice Have Enhanced Osteoclast Differentiation and Differentially Regulated Gene Expression Compared to Femur-Derived Monocytes
by Emilyn D. Asinas, Rachel Clark, Jadyn Nelson, Juan E. Abrahante Llorens, Kim Mansky and Amy Tasca
Biology 2025, 14(3), 273; https://doi.org/10.3390/biology14030273 - 7 Mar 2025
Viewed by 444
Abstract
It is well established that both men and women lose bone as they age. While recent studies suggest unique molecular signatures of mineral-resorbing cells at different anatomical locations, most studies focus on long bones, and little is known about craniofacial osteoclasts, especially during [...] Read more.
It is well established that both men and women lose bone as they age. While recent studies suggest unique molecular signatures of mineral-resorbing cells at different anatomical locations, most studies focus on long bones, and little is known about craniofacial osteoclasts, especially during the aging process. To determine differences between osteoclasts at different skeletal sites, we analyzed the differentiation potential, demineralization activity, and gene expression of osteoclast precursors from 1-year-old male and female C57Bl/6J mice. In our study, we determined that mandibular-derived osteoclasts were larger in size compared to those in the femur but were significantly fewer in number. However, femur-derived osteoclasts demineralized larger and more numerous areas of a calcium phosphate surface compared to mandibular-derived osteoclasts. Bulk RNA sequencing demonstrated that the mandibular-derived monocytes were enriched for genes in the WNT signaling pathway, biomineralization, and osteogenesis pathways, while femur-derived monocytes were enriched for genes in the mitochondrial respiratory complex I. Overall, our data suggest that there are different mechanisms that regulate osteoclasts from different skeletal sites as we age. This information may help to guide the design of treatments to prevent aging-induced bone loss. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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14 pages, 1632 KiB  
Article
Cannabis (THC) Aggravates the Deleterious Effects of Alcohol (EtOH) on Skeletal Muscles’ Mitochondrial Respiration: Modulation by Age and Metabolic Phenotypes
by Anne-Laure Charles, Margherita Giannini, Alain Meyer, Anne Charloux, Samy Talha, Thomas Vogel, Jean-Sébastien Raul, Valérie Wolff and Bernard Geny
Biology 2024, 13(12), 1080; https://doi.org/10.3390/biology13121080 - 21 Dec 2024
Cited by 1 | Viewed by 1339
Abstract
The anti-inflammatory and analgesic properties of cannabis might be useful to treat muscle diseases, including those linked or not to alcohol. Nevertheless, delta 9 tetrahydrocannabinol (THC) and ethanol (EtOH), often used concomitantly, can have deleterious effects on cardiac mitochondria. We therefore determined whether [...] Read more.
The anti-inflammatory and analgesic properties of cannabis might be useful to treat muscle diseases, including those linked or not to alcohol. Nevertheless, delta 9 tetrahydrocannabinol (THC) and ethanol (EtOH), often used concomitantly, can have deleterious effects on cardiac mitochondria. We therefore determined whether EtOH, alone and associated with THC, impairs skeletal muscle mitochondrial respiration. Further, we investigated potential modulation by metabolic phenotype and age by analyzing predominantly glycolytic gastrocnemius and oxidative soleus muscles in young and middle-aged rats (12 and 49 weeks). Considering the gastrocnemius, EtOH impaired mitochondrial respiration in a similar manner in young- and middle-aged muscles (−34.97 ± 2.97% vs. −37.50 ± 6.03% at 2.1 × 10−5 M; p < 0.05). Interestingly, concomitant THC aggravated EtOH-related mitochondrial impairment in young gastrocnemius (−49.92 ± 1.69%, vs. −34.97 ± 2.97 p < 0.05). Concerning the soleus, EtOH alone mainly decreased young muscle mitochondrial respiration (−42.39 ± 2.42% vs. −17.09 ± 7.61% at 2.1 × 10−5 M, p < 0.001, at 12 and 49 weeks). The soleus was less impaired at 12 weeks by THC and EtOH association than the gastrocnemius (−49.92 ±1.69 vs. −27.22 ± 8.96% in gastrocnemius and soleus, respectively, p < 0.05). In conclusion, EtOH, alone and associated with THC, significantly impairs skeletal muscle mitochondrial respiration and THC aggravates EtOH-induced effects on young glycolytic muscle. Age and metabolic phenotypes modulate these deleterious effects, with the glycolytic muscles of young rats being more prone to impairments than oxidative muscles. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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15 pages, 3425 KiB  
Article
The Functional and Anatomical Impacts of Healthy Muscle Ageing
by James P. Charles and Karl T. Bates
Biology 2023, 12(10), 1357; https://doi.org/10.3390/biology12101357 - 23 Oct 2023
Cited by 1 | Viewed by 2348
Abstract
Even “healthy” muscle ageing is often associated with substantial changes in muscle form and function and can lead to increased injury risks and significant negative impacts on quality of life. However, the impacts of healthy muscle ageing on the fibre architecture and microstructure [...] Read more.
Even “healthy” muscle ageing is often associated with substantial changes in muscle form and function and can lead to increased injury risks and significant negative impacts on quality of life. However, the impacts of healthy muscle ageing on the fibre architecture and microstructure of different muscles and muscle groups throughout the lower limb, and how these are related to their functional capabilities, are not fully understood. Here, a previously established framework of magnetic resonance and diffusion tensor imaging was used to measure the muscle volumes, intramuscular fat, fibre lengths and physiological cross-sectional areas of 12 lower limb muscles in a cohort of healthily aged individuals, which were compared to the same data from a young population. Maximum muscle forces were also measured from an isokinetic dynamometer. The more substantial interpopulation differences in architecture and functional performance were located within the knee extensor muscles, while the aged muscles were also more heterogeneous in muscle fibre type and atrophy. The relationships between architecture and muscle strength were also more significant in the knee extensors compared to other functional groups. These data highlight the importance of the knee extensors as a potential focus for interventions to negate the impacts of muscle ageing. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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14 pages, 3744 KiB  
Article
ProBDNF Upregulation in Murine Hind Limb Ischemia Reperfusion Injury: A Driver of Inflammation
by Katherine Aby, Ryan Antony and Yifan Li
Biology 2023, 12(7), 903; https://doi.org/10.3390/biology12070903 - 24 Jun 2023
Cited by 4 | Viewed by 1723
Abstract
Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor [...] Read more.
Brain-derived neurotropic factor (BDNF) has been shown to be expressed in many nonneuronal tissues including skeletal muscle. Skeletal muscle BDNF has been studied regarding its function in metabolism and exercise; however, less is known about its role in skeletal muscle injury. The precursor to BDNF, proBDNF, has an unknown role in skeletal muscle. The levels of proBDNF, mature BDNF, and their receptors were compared in the skeletal muscle and brain tissues of C57BL/6J mice. Tourniquet-induced hind limb ischemia-reperfusion injury was used to assess the function of skeletal muscle-derived proBDNF in skeletal muscle injury. Skeletal muscle-specific knockout of BDNF and pharmacological inhibition of p75NTR, the proBDNF receptor, were used to determine the role of proBDNF–p75NTR signaling. We show for the first time that proBDNF is the predominantly expressed form of BDNF in skeletal muscle and that proBDNF is significantly upregulated in skeletal muscle following hind limb ischemia-reperfusion injury. Skeletal muscle-specific knockout of BDNF blunted the inflammatory response in the injured tissue and appears to be mediated by the proBDNF–p75NTR pathway, as shown by the pharmacological inhibition of p75NTR. These findings suggest that skeletal muscle proBDNF plays a critical role in driving the inflammatory response following skeletal muscle injury. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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12 pages, 2393 KiB  
Article
Role of Muscle Ultrasound for the Study of Frailty in Elderly Patients with Diabetes: A Pilot Study
by Andreu Simó-Servat, Ernesto Guevara, Verónica Perea, Núria Alonso, Carmen Quirós, Carlos Puig-Jové and María-José Barahona
Biology 2023, 12(6), 884; https://doi.org/10.3390/biology12060884 - 19 Jun 2023
Cited by 6 | Viewed by 2696
Abstract
Background: Sarcopenia and diabetes contribute to the development of frailty. Therefore, accessible methods, such as muscle ultrasounds (MUSs), to screen for sarcopenia should be implemented in clinical practice. Methods: We conducted a cross-sectional pilot study including 47 patients with diabetes (mean age: 77.72 [...] Read more.
Background: Sarcopenia and diabetes contribute to the development of frailty. Therefore, accessible methods, such as muscle ultrasounds (MUSs), to screen for sarcopenia should be implemented in clinical practice. Methods: We conducted a cross-sectional pilot study including 47 patients with diabetes (mean age: 77.72 ± 5.08 years, mean weight: 75.8 kg ± 15.89 kg, and body mass index: 31.19 ± 6.65 kg/m2) categorized as frail by the FRAIL Scale or Clinical Frailty Scale and confirmed by Fried’s Frailty Phenotype or Rockwood’s 36-item Frailty Index. We used the SARC-F questionnaire to identify sarcopenia. The Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) tests were used to assess physical performance and the risk of falls, respectively. In addition, other variables were measured: fat-free mass (FFM) and Sarcopenia Risk Index (SRI) with the bioimpedance analysis (BIA); thigh muscle thickness (TMT) of the quadriceps with MUS; and hand-grip strength with dynamometry. Results: We observed correlations between the SARC-F and FFM (R = −0.4; p < 0.002) and hand-grip strength (R = −0.5; p < 0.0002), as well as between the TMT and FFM of the right leg (R = 0.4; p < 0.02) and the SRI (R = 0.6; p < 0.0001). We could predict sarcopenia using a logistic regression model with a ROC curve (AUC = 0.78) including FFM, handgrip strength, and TMT. The optimal cut-off point for maximum efficiency was 1.58 cm for TMT (sensitivity = 71.4% and specificity = 51.5%). However, we did not observe differences in the TMT among groups of greater/less frailty based on the SARC-F, SPPB, and TUG (p > 0.05). Conclusions: MUSs, which correlated with the BIA (R = 0.4; p < 0.02), complemented the diagnosis, identifying regional sarcopenia of the quadriceps in frail patients with diabetes and improving the ROC curve to AUC = 0.78. In addition, a TMT cut-off point for the diagnosis of sarcopenia of 1.58 cm was obtained. Larger studies to validate the MUS technique as a screening strategy are warranted. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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11 pages, 995 KiB  
Article
Sarcopenia Is Associated with an Increased Risk of Postoperative Complications Following Total Hip Arthroplasty for Osteoarthritis
by Kenny Chang, J. Alex Albright, Edward J. Testa, Alanna B. Balboni, Alan H. Daniels and Eric Cohen
Biology 2023, 12(2), 295; https://doi.org/10.3390/biology12020295 - 13 Feb 2023
Cited by 11 | Viewed by 3773
Abstract
Sarcopenia is a state of catabolic muscle wasting prevalent in geriatric patients. Likewise, osteoarthritis is an age-related musculoskeletal disease affecting patients with similar demographics. Late-stage hip osteoarthritis is often treated with total hip arthroplasty (THA). As sarcopenia influences the surgical outcomes, this study [...] Read more.
Sarcopenia is a state of catabolic muscle wasting prevalent in geriatric patients. Likewise, osteoarthritis is an age-related musculoskeletal disease affecting patients with similar demographics. Late-stage hip osteoarthritis is often treated with total hip arthroplasty (THA). As sarcopenia influences the surgical outcomes, this study aimed to assess the impact of sarcopenia on the outcomes of THA. A 1:3 matched case–control study of sarcopenic to control patients was performed using a large national database. In total, 3992 patients were analyzed. Sarcopenic patients undergoing THA were more likely to experience dislocation (odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.21–3.91) within 1 year of THA. Furthermore, sarcopenic patients had higher urinary tract infection rates (OR = 1.79, CI 1.32–2.42) and a greater risk of 90-day hospital readmission (hazard ratio (HR) = 1.39, CI 1.10–1.77). Sarcopenic patients experienced more falls (OR = 1.62, CI 1.10–2.39) and fragility fractures (OR = 1.77, CI 1.34–2.31). Similarly, sarcopenic patients had higher day of surgery costs (USD 13,534 vs. USD 10,504) and 90-day costs (USD 17,139 vs. USD 13,394) compared with the controls. Ultimately, sarcopenic patients undergoing THA experience higher rates of postoperative complications and incur greater medical costs. Given the potential risks, orthopedic surgeons may consider treating or reducing the severity of sarcopenia before surgery. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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10 pages, 2293 KiB  
Brief Report
Gait Asymmetry and Post-Traumatic Osteoarthritis Following Anterior Cruciate Ligament Rupture: A Preliminary Study
by Samuel Pringle and Kristiaan D’Août
Biology 2025, 14(2), 208; https://doi.org/10.3390/biology14020208 - 16 Feb 2025
Viewed by 551
Abstract
Knee post-traumatic osteoarthritis (PTOA) often develops in younger populations following anterior cruciate ligament (ACL) rupture, accounting for 12% of all symptomatic osteoarthritis (OA). The current literature implicates gait asymmetry in late-stage knee OA progression; however, early-knee PTOA development involvement is ill defined. This [...] Read more.
Knee post-traumatic osteoarthritis (PTOA) often develops in younger populations following anterior cruciate ligament (ACL) rupture, accounting for 12% of all symptomatic osteoarthritis (OA). The current literature implicates gait asymmetry in late-stage knee OA progression; however, early-knee PTOA development involvement is ill defined. This study explored gait asymmetry involvement in early-stage knee PTOA following ACL ruptures. Gait asymmetry, measured as asymmetry in duty factor (relative contact time), and joint loading data were collected, using infrared-camera motion capture and Kistler force plates for participants exhibiting either historical ACL ruptures (ACL+; n = 4) or no previous joint trauma (ACL−; n = 11). Joint loading measures included external knee adduction moment (EKAM) and external knee flexion moment (KFM), early (peak 1; EKAMp1 and KFMp1) and late (peak 2; EKAMp2 and KFMp2), stance peaks (Nm/kg), and respective time integrals (Nm·ms/kg; iEKAMp1, iEKAMp2, iKFMp1, and iKFMp2). ACL+ exhibited greater asymmetrical duty factor (78% difference) and greater joint load differences: EKAMp1 (26%), EKAMp2 (49%), KFMp1 (37%), iKFMp1 (44%), and iKFMp2 (60%). Significant relationships were found between duty factor asymmetry and both KFMp2 (R2 = 0.665) and iKFMp2 (R2 = 0.504). These preliminary data suggest gait asymmetry-induced joint loading may contribute to knee PTOA progression, but further research with increased sample sizes and the quantitative assessment of cartilage status is required. Full article
(This article belongs to the Special Issue Musculoskeletal Biology: Impact of Ageing and Disease)
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