Molecular Mechanisms and Novel Diagnostic and Therapeutic Approaches of Musculoskeletal Disease

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 13149

Special Issue Editors


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Guest Editor
Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan
Interests: orthopedic surgery; stem cell biology; cancer immunotherapy

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Guest Editor
Department of Orthopedic Surgery, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
Interests: orthopedic surgery; arthroplasty surgery; osteoporosis research; osteoarthritis research

Special Issue Information

Dear Colleagues,

Musculoskeletal diseases (e.g., osteoarthritis, osteoporosis, deformities, inflammatory disorders, infection, and neoplasm) are prevalent in clinical settings, with growing medical expenditure. This Special Issue attempts to provide novel information that could potentially resolve the present unmet needs in aspects of molecular mechanisms and novel diagnostic as well as therapeutic approaches in musculoskeletal diseases. Manuscripts covering the following aspects are of special interest to the editor:

  1. The mechanisms of therapeutic resistance of musculoskeletal neoplasm under present treatments (e.g., the mechanisms underlying the resistance of sarcoma to immune checkpoint blockades).
  2. Novel diagnostic or treatment-stratifying approaches for all kinds of musculoskeletal disorders. The application of artificial intelligence (deep learning) is of special interest to the editor.
  3. The application of stem cells, bioprinting, and nanotechnology in the treatment of musculoskeletal diseases.
  4. CAOS (computer-assisted orthopedic surgery).
  5. Big data analytic (populated-based) studies for musculoskeletal diseases.

Dr. Shu-Jui Kuo
Prof. Dr. Jih-Yang Ko
Guest Editors

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Keywords

  • immune checkpoint blockade
  • artificial intelligence (deep learning)
  • stem cell
  • bioprinting
  • nanotechnology
  • CAOS (computer-assisted orthopedic surgery)

Published Papers (8 papers)

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Research

12 pages, 2755 KiB  
Article
Comparison between Novel Anatomical Locking Guide Plate and Conventional Locking Plate for Acetabular Fractures: A Finite Element Analysis
by Xiao Liu, Jianpeng Gao, Xiaoyong Wu, Junhao Deng, Zijian Li, Ran Li, Licheng Zhang, Jianheng Liu and Ming Li
Life 2023, 13(11), 2108; https://doi.org/10.3390/life13112108 - 24 Oct 2023
Viewed by 732
Abstract
The treatment of complex acetabular fractures remains a complicated clinical challenge. Our self-designed novel anatomical locking guide plate (NALGP) has previously shown promising potential in T-shaped acetabular fractures (TAF), but a direct comparison with conventional fixations is yet to be made. The TAF [...] Read more.
The treatment of complex acetabular fractures remains a complicated clinical challenge. Our self-designed novel anatomical locking guide plate (NALGP) has previously shown promising potential in T-shaped acetabular fractures (TAF), but a direct comparison with conventional fixations is yet to be made. The TAF model was established based on a volunteer’s computer tomography data and then fixed with double column locking plates (DLP), a posterior column locking plate with anterior column screws (LPACS), and our NALGP. Forces of 200 N, 400 N, and 600 N were then loaded on the model vertically downward, respectively. The stress distribution and peaks and maximum displacements at three sites were assessed. We found that the stress area of all three plates was mainly concentrated around the fracture line, while only the matching screws of the NALGP showed no obvious stress concentration points. In addition, the NALGP and DLP showed significantly less fracture fragment displacement than the LPACS at the three main fracture sites. The NALGP was found to have less displacement than DLP at the posterior column and ischiopubic branch sites, especially under the higher loading forces of 400 N and 600 N. The fixation stability of the NALGP for TAF was similar to that of DLP but better than that of LPACS. Moreover, the NALGP and its matching screws have a more reasonable stress distribution under different loads of force and the same strength as the LPACS. Full article
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15 pages, 4351 KiB  
Article
Changes in Serum Bone Metabolism Markers after Living Donor Liver Transplantation (LDLT) and Their Association with Fracture Occurrences
by Shu-Jui Kuo, Chao-Long Chen, Sung-Hsiung Chen and Jih-Yang Ko
Life 2023, 13(7), 1438; https://doi.org/10.3390/life13071438 - 25 Jun 2023
Cited by 2 | Viewed by 879
Abstract
Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and femoral neck T scores, along with bone resorption marker reductions and liver regeneration [...] Read more.
Living donor liver transplantation (LDLT) is lifesaving, but can lead to osteoporosis and fractures. In our 3-year study of 25 LDLT recipients, we observed significant reductions in lumbar spine and femoral neck T scores, along with bone resorption marker reductions and liver regeneration marker increases. Serum calcium levels increased, while osteoprotegerin (OPG) decreased and Dickkopf-related protein 1 (DKK-1) increased. Patients who suffered fractures within 3 years of LDLT had higher serum OPG, lower serum nuclear factor kappa B ligand (RANKL), a higher OPG/RANKL ratio and higher serum DKK-1 levels. OPG, RANKL, OPG/RANKL ratio and DKK-1 levels before LDLT predicted hip or spine fractures within three years after LDLT. Further research is necessary to determine the optimal level of osteoclastic activity for preventing fracture onset. Full article
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14 pages, 929 KiB  
Article
Hip and Knee Osteoarthritis in Patients with Chronic Myeloproliferative Neoplasms: A Cross-Sectional Study
by Hrvoje Holik, Ivan Krečak, Marko Lucijanić, Ivan Samardžić, Danijel Pilipac, Ivana Vučinić Ljubičić, Božena Coha, Alma Kitter Pipić, Blaženka Miškić and Silva Zupančić-Šalek
Life 2023, 13(6), 1388; https://doi.org/10.3390/life13061388 - 14 Jun 2023
Cited by 3 | Viewed by 1515
Abstract
Background: Osteoarthritis (OA) is a progressive degenerative disease with an inflammatory background. Chronic myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by chronic inflammation and a tendency for connective tissue remodeling. Aim: This study aimed to investigate the prevalence and associated risk factors [...] Read more.
Background: Osteoarthritis (OA) is a progressive degenerative disease with an inflammatory background. Chronic myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by chronic inflammation and a tendency for connective tissue remodeling. Aim: This study aimed to investigate the prevalence and associated risk factors of symptomatic OA (sOA) in MPN patients. Patients and methods: A total of 100 consecutive MPN (39 essential-thrombocythemia, 34 polycythemia-vera, 27 myelofibrosis) patients treated in two community hematologic centers were cross-sectionally evaluated. Patients were required to have both symptoms attributable to hip and/or knee OA and radiographic confirmation to be considered as having sOA. Results: The prevalence of hip and/or knee sOA was significantly higher among MPN patients than the previously reported prevalence in the general population of similar age (61% vs. 22%, p < 0.001). Hip sOA was present in 50%, knee sOA in 51% and sOA of both localizations in 41% of patients. A high proportion of MPN patients had radiographic signs of hip OA (94%) and knee OA (98%) in the presence of attributable symptoms. Among the other factors, sOA was univariately associated with the presence of JAK2 mutation, myelofibrosis phenotype, older age, higher body weight, and higher MPN-SAF score (p < 0.050 for all analyses). In the multivariate analysis, older age (odds ratio = 1.19, 95% confidence interval-CI 1.06–1.33) and higher body weight (OR = 1.15, 95% CI 1.06–1.25) were recognized as independent risk factors for sOA. On the other hand, cytoreductive treatment was a protective factor for sOA (OR = 0.07, 95% CI 0.006–0.86). Conclusions: The prevalence of sOA in MPN patients was higher than that in the general population and seems to correlate with older age, increased myeloproliferation and a higher inflammatory state. Whether cytoreductive treatment may postpone OA development in MPN patients warrants additional confirmation. Full article
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11 pages, 1066 KiB  
Article
Detection of Angiogenic T Cells and Endothelial Progenitor Cells in Behçet Disease and Determination of Their Relationship with Disease Activity
by Ayhan Kul, Nurinnisa Ozturk, Asli Koseoglu Kurt and Yasar Arslan
Life 2023, 13(6), 1259; https://doi.org/10.3390/life13061259 - 25 May 2023
Viewed by 938
Abstract
Angiogenic T (Tang) cells and endothelial progenitor cells (EPCs) play a role in maintaining vascular integrity and repair. This study considers the association between them and Behçet disease (BD) and disease activity. Fifty patients with BD and forty-five age- and gender-matched healthy controls [...] Read more.
Angiogenic T (Tang) cells and endothelial progenitor cells (EPCs) play a role in maintaining vascular integrity and repair. This study considers the association between them and Behçet disease (BD) and disease activity. Fifty patients with BD and forty-five age- and gender-matched healthy controls were included in the study. The participants’ demographic, clinical, and laboratory characteristics were recorded, and their blood Tang cell and EPC counts were determined. Fifty patients were diagnosed with BD, consisting of 24 females and 26 males. The blood Tang cell (3.5 ± 1.2 cells/μL in patients, 4 ± 0.9 cells/μL in controls, p = 0.046)) and EPC (2.9 ± 0.9 cells/μL in patients, 3.7 ± 1 cells/μL in controls, p = 0.001) counts were significantly lower for the patient group with BD than for the control group. The blood Tang cell (42.5 ± 4.9% in active patients, 48.9 ± 7.9% in inactive patients, p = 0.001) and EPC (35.5 ± 6.4% in active patients, 41.2 ± 6.3% in inactive patients, p = 0.004) levels were lower for the patient group with active BD than for the inactive patient group. A weak positive correlation was present between the blood Tang cell and EPC percentage values in BD (r: 0.318, p = 0.002). It was determined that Tang cell and EPC counts are lower in BD, and these reductions become more profound with increasing disease activity. This situation may prevent the development of a sufficient immune response against a disease with a course of chronic inflammation or may trigger the formation of autoreactive immunity. A reduction in Tang cells and EPCs may serve as a marker or predictor of vascular damage in BD patients and represents the progression of vascular injury. Full article
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10 pages, 244 KiB  
Article
The Impact of Physical Activity on Adolescent Idiopathic Scoliosis
by Josipa Glavaš, Mirjana Rumboldt, Željka Karin, Roberta Matković, Vesna Bilić-Kirin, Vesna Buljan, Tanja Obelić-Babok and Jure Aljinović
Life 2023, 13(5), 1180; https://doi.org/10.3390/life13051180 - 13 May 2023
Cited by 1 | Viewed by 2376
Abstract
The prevalence of adolescent idiopathic scoliosis (AIS) is increasing, partly due to a lack of physical activity. In a cross-sectional study with 18,216 pupils (5th, 6th, and 8th grades) from four Croatian counties using the forward bend test (FBT; presumed AIS), the prevalence [...] Read more.
The prevalence of adolescent idiopathic scoliosis (AIS) is increasing, partly due to a lack of physical activity. In a cross-sectional study with 18,216 pupils (5th, 6th, and 8th grades) from four Croatian counties using the forward bend test (FBT; presumed AIS), the prevalence of AIS and its correlation with physical activity were evaluated. Pupils with presumed AIS were less physically active than their peers without scoliosis (p < 0.001). Abnormal FBT was more prevalent among girls than boys (8.3% vs. 3.2%). Boys were more physically active than girls (p < 0.001). Pupils with presumed AIS were less physically active than their peers without scoliosis (p < 0.001). A higher prevalence of presumed AIS was found among inactive or just recreationally active schoolchildren than among those engaged in organized sports (p = 0.001), girls especially. Pupils with presumed AIS were less active and had fewer weekly sports sessions than their peers without scoliosis (p < 0.001). Notably low prevalence of AIS was detected among pupils engaged in soccer (2.8%, p < 0.001), handball (3.4%, p = 0.002), and martial arts (3.9%, p = 0.006), while it was higher than expected in swimming (8.6%, p = 0.012), dancing (7.7%, p = 0.024), and volleyball (8.2%, p = 0.001) participants. No difference was detected for other sports. A positive correlation was found between time spent using handheld electronic devices and the prevalence of scoliosis (rs = 0.06, p < 0.01). This study confirms the increasing prevalence of AIS, particularly among less athletic girls. Further, prospective studies in this field are required to explain whether the higher prevalence of AIS in these sports is due to referral or other aspects. Full article
27 pages, 6135 KiB  
Article
Diversity and Differential Expression of MicroRNAs in the Human Skeletal Muscle with Distinct Fiber Type Composition
by Andrey V. Zhelankin, Liliia N. Iulmetova, Ildus I. Ahmetov, Eduard V. Generozov and Elena I. Sharova
Life 2023, 13(3), 659; https://doi.org/10.3390/life13030659 - 28 Feb 2023
Cited by 4 | Viewed by 2213
Abstract
The ratio of fast- and slow-twitch fibers in human skeletal muscle is variable and largely determined by genetic factors. In this study, we investigated the contribution of microRNA (miRNA) in skeletal muscle fiber type composition. The study involved biopsy samples of the vastus [...] Read more.
The ratio of fast- and slow-twitch fibers in human skeletal muscle is variable and largely determined by genetic factors. In this study, we investigated the contribution of microRNA (miRNA) in skeletal muscle fiber type composition. The study involved biopsy samples of the vastus lateralis muscle from 24 male participants with distinct fiber type ratios. The miRNA study included samples from five endurance athletes and five power athletes with the predominance of slow-twitch (61.6–72.8%) and fast-twitch (69.3–80.7%) fibers, respectively. Total and small RNA were extracted from tissue samples. Total RNA sequencing (N = 24) revealed 352 differentially expressed genes between the groups with the predominance of fast- and slow-twitch muscle fibers. Small RNA sequencing showed upregulation of miR-206, miR-501-3p and miR-185-5p, and downregulation of miR-499a-5p and miR-208-5p in the group of power athletes with fast-twitch fiber predominance. Two miRtronic miRNAs, miR-208b-3p and miR-499a-5p, had strong correlations in expression with their host genes (MYH7 and MYH7B, respectively). Correlations between the expression of miRNAs and their experimentally validated messenger RNA (mRNA) targets were calculated, and 11 miRNA–mRNA interactions with strong negative correlations were identified. Two of them belonged to miR-208b-3p and miR-499a-5p, indicating their regulatory links with the expression of CDKN1A and FOXO4, respectively. Full article
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10 pages, 1463 KiB  
Communication
Effects of E’Jiao on Skeletal Mineralisation, Osteocyte and WNT Signalling Inhibitors in Ovariectomised Rats
by Kok-Yong Chin, Ben Nett Ng, Muhd Khairik Imran Rostam, Nur Farah Dhaniyah Muhammad Fadzil, Vaishnavi Raman, Farzana Mohamed Yunus, Wun Fui Mark-Lee, Yan Yi Chong, Jing Qian, Yan Zhang, Haibin Qu, Syed Alhafiz Syed Hashim and Sophia Ogechi Ekeuku
Life 2023, 13(2), 570; https://doi.org/10.3390/life13020570 - 17 Feb 2023
Cited by 2 | Viewed by 1605
Abstract
E’Jiao is a traditional Chinese medicine derived from donkey skin. E’Jiao is reported to suppress elevated bone remodelling in ovariectomised rats but its mechanism of action is not known. To bridge this research gap, the current study aims to investigate the effects of [...] Read more.
E’Jiao is a traditional Chinese medicine derived from donkey skin. E’Jiao is reported to suppress elevated bone remodelling in ovariectomised rats but its mechanism of action is not known. To bridge this research gap, the current study aims to investigate the effects of E’Jiao on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. Female Sprague–Dawley rats (3 months old) were ovariectomised and supplemented with E’Jiao at 0.26 g/kg, 0.53 g/kg and 1.06 g/kg, or 1% calcium carbonate (w/v) in drinking water. The rats were euthanised after two months of supplementation and their bones were collected for Fourier-transform infrared spectroscopy, histomorphometry and protein analysis. Neither ovariectomy nor treatment affected the skeletal mineral/matrix ratio, osteocyte number, empty lacunar number, and Dickkopf-1 and sclerostin protein levels (p > 0.05). Rats treated with calcium carbonate had a higher Dickkopf-1 level than baseline (p = 0.002) and E’Jiao at 0.53 g/kg (p = 0.002). In conclusion, E’Jiao has no significant effect on skeletal mineralisation, osteocyte and WNT signalling inhibitors in ovariectomised rats. The skeletal effect of E’Jiao might not be mediated through osteocytes. Full article
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13 pages, 4628 KiB  
Article
Decreased Expression of Leptin among Patients with Shoulder Stiffness
by Jih-Yang Ko, Sung-Hsiung Chen, Re-Wen Wu, Kuan-Ting Wu, Chieh-Cheng Hsu and Shu-Jui Kuo
Life 2022, 12(10), 1588; https://doi.org/10.3390/life12101588 - 12 Oct 2022
Cited by 4 | Viewed by 1418
Abstract
Shoulder stiffness (SS) is a disease that is fibroblastic and inflammatory in nature. Leptin is an adipokine-mediating the fibroblastic and inflammatory processes of various diseases. Our study tried to investigate the role of leptin in SS pathogenesis. Subacromial bursa from stiff and non-stiff [...] Read more.
Shoulder stiffness (SS) is a disease that is fibroblastic and inflammatory in nature. Leptin is an adipokine-mediating the fibroblastic and inflammatory processes of various diseases. Our study tried to investigate the role of leptin in SS pathogenesis. Subacromial bursa from stiff and non-stiff shoulders were obtained for reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunoblotting. Subacromial fluid was obtained for enzyme-linked immunosorbent assay. We showed that the expression level of leptin was lower in the subacromial bursae from the stiff shoulders in RT-PCR analysis (p < 0.001) and immunoblotting (p < 0.001). The concentration of leptin was also lower in the subacromial fluid derived from stiff shoulders. The leptin level in the subacromial fluid was positively associated with the constant score, total range of motion, flexion, abduction, and external rotation. The synovial fibroblasts derived from stiff shoulder-retrieved subacromial bursa were treated by 0, 1, and 3 μM leptin. Under RT-qPCR analysis, leptin was shown to dose-dependently decrease the transcription of IL-6, IL-10, and IL-13, but without impact on IL-1β and IL-4 (p < 0.001, p = 0.001, p = 0.001, p = 0.137, and p = 0.883 by ANOVA test, respectively). These results shed light on the role of leptin in orchestrating the disease processes of SS. Full article
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