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New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration
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New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 16254

Special Issue Editors

Dr. Francesco Grassi

E-Mail Website
Guest Editor
RAMSES Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Interests: bone metabolism and bone tissue regeneration; pathogenesis of osteoporosis; pharmacological and non pharmacological treatment of bone-wasting diseases
Dr. Laura Gambari

E-Mail Website
Guest Editor
Laboratorio Ramses, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Interests: role of Hydrogen sulphide in cell and tissue regulation in physiology and pathology; bone and cartilage physiopathology; bone remodelling (osteoclastogenesis, osteoblastogenesis); osteoporosis; osteoarthritis; regenerative medicine and tissue engineering

Special Issue Information

Dear Colleagues,

Musculoskeletal diseases (MSDs), which include but are not limited to osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, ankylosing spondylitis, chronic lower back pain, and chronic degenerative lesions of the spine, are one of the major global health concerns for both individuals and societies. Despite their different etiologies and pathophysiology, the majority of MSDs are characterized by chronic pain due to destructive inflammatory processes that can lead to impaired mobility, severe disabilities and premature death. Moreover, specific alterations in pathways involved in tissue regeneration predispose individuals to hampered integration, regeneration, and healing of bone and cartilage substitutes and impaired in situ guided tissue regeneration when necessary.

Current pharmacological drugs help patients to manage their condition and symptoms; however, only a few are effective disease modifying drugs. The discovery of effective therapeutics for MSDs is desperately needed given that they are mostly associated with ageing and are predicted to steadily increase by 2050, along with the growth of the elderly population. Furthermore, a present stimulating challenge is the development of strategies aimed at improving bone or cartilage regeneration in the context of MSDs.

Along with pharmacological treatments, complementary therapies have gained increased attention due to their analgesic, anti-inflammatory, immune-modulating effects and promotion of specific processes involved in cartilage and bone regeneration. Likewise, new strategies for improving bone and cartilage regeneration by functionalization with natural compounds have recently emerged.

This Special Issue intends to attract high-quality research on non-pharmacological approaches to MSDs to boost integration among researchers, practitioners, bio-engineers, and health scientists in the field.

Potential topics include, but are not limited to, nutraceuticals, active ingredients of plants, nutrition, and naturally derived molecules for functionalizing biomaterials.

We invite authors to propose original research, review articles and communications highlighting:

  • evidence of mechanism of action and effectiveness of nutraceuticals and biomolecules
  • identification of novel molecules to be used as a non-pharmacological approach to specific MSDs;
  • identification of specific components of plant materials that target specific pathological pathways involved in MSDs;
  • validation of biomarkers able to trace response to treatments of MSDs with complementary therapies;
  • novel in vitro and in vivo models to assess the efficacy of complementary therapies.

We welcome systematic reviews on topics including but not limited to:

  • important issues related to the prevention, diagnosis and therapy of MSDs;
  • updates of efficacy of classes of molecules related to complementary therapy;
  • novel concepts on support therapies and nutrition-based prevention of MSDs;
  • harmonization and standardization of protocols for treatments of specific MSDs;
  • updates on biomarkers able to help with diagnosis, trace symptoms and progression, response to treatments of MSDs;
  • scaffold functionalization with natural compounds. 

Finally, given the recently renewed interest in the role of balneological treatments for MSDs, manuscripts and reviews focusing on the identification of specific components of thermal mineral water that targets specific pathological pathways of MSDs, or more generally on the role of balneology in MSDs, are within the scope of this Special Issue.

Dr. Francesco Grassi
Dr. Laura Gambari
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. 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

  • complementary therapies
  • nutraceuticals
  • osteoarthritis
  • rheumatoid arthritis
  • osteoporosis
  • fibromyalgia
  • ankylosing spondylitis
  • chronic low back pain
  • chronic degenerative lesions
  • balneology
  • nutraceuticals
  • regenerative medicines

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

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Research

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24 pages, 3716 KiB  
Article
Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials
by Chun-De Liao, Hung-Chou Chen, Mao-Hua Huang, Tsan-Hon Liou, Che-Li Lin and Shih-Wei Huang
Int. J. Mol. Sci. 2023, 24(7), 6078; https://doi.org/10.3390/ijms24076078 - 23 Mar 2023
Cited by 10 | Viewed by 5568
Abstract
Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven [...] Read more.
Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = −2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (β = −2.52) and WC (β = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity. Full article
(This article belongs to the Special Issue New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration)
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13 pages, 5391 KiB  
Article
Reactivation of Vertebral Growth Plate Function in Vertebral Body Tethering in an Animal Model
by Michał Latalski, Tomasz Szponder, Grzegorz Starobrat, Edward Warda, Magdalena Wójciak, Sławomir Dresler, Anna Danielewicz, Jan Sawicki and Ireneusz Sowa
Int. J. Mol. Sci. 2022, 23(19), 11596; https://doi.org/10.3390/ijms231911596 - 30 Sep 2022
Viewed by 2344
Abstract
Flexible spine tethering is a relatively novel fusionless surgical technique that aims to correct scoliosis based on growth modulation due to the pressure exerted on the vertebral body epiphyseal growth plate. The correction occurs in two phases: immediate intraoperative and postoperative with growth. [...] Read more.
Flexible spine tethering is a relatively novel fusionless surgical technique that aims to correct scoliosis based on growth modulation due to the pressure exerted on the vertebral body epiphyseal growth plate. The correction occurs in two phases: immediate intraoperative and postoperative with growth. The aim of this study was to evaluate the reactivation of vertebral growth plate function after applying corrective forces. The rat tail model was used. Asymmetric compression and distraction of caudal growth plates were performed using a modified external fixation apparatus. Radiological and histopathological data were analysed. After three weeks of correction, the activity of the structures increased across the entire growth plate width, and the plate was thickened. The height of the hypertrophic layer and chondrocytes on the concave side doubled in height. The height of chondrocytes and the cartilage thickness on the concave and central sides after the correction did not differ statistically significantly from the control group. Initiation of the correction of scoliosis in the growing spine, with relief of the pressure on the growth plate, allows the return of the physiological activity of the growth cartilage and restoration of the deformed vertebral body. Full article
(This article belongs to the Special Issue New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration)
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13 pages, 2895 KiB  
Article
Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats
by Mahmoud E. Youssef, Mustafa A. Abdel-Reheim, Mohamed A. Morsy, Mahmoud El-Daly, Gamal M. K. Atwa, Galal Yahya, Simona Cavalu, Sameh Saber and Ahmed Gaafar Ahmed Gaafar
Int. J. Mol. Sci. 2022, 23(18), 10297; https://doi.org/10.3390/ijms231810297 - 7 Sep 2022
Cited by 12 | Viewed by 2499
Abstract
Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined [...] Read more.
Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund’s adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat’s hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor–kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis. Full article
(This article belongs to the Special Issue New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration)
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22 pages, 1724 KiB  
Article
Manual Therapy Facilitates Homeostatic Adaptation to Bone Microstructural Declines Induced by a Rat Model of Repetitive Forceful Task
by Mary F. Barbe, Mamta Amin, Michele Y. Harris, Siva Tejaa Panibatla, Soroush Assari, Steven N. Popoff and Geoffrey M. Bove
Int. J. Mol. Sci. 2022, 23(12), 6586; https://doi.org/10.3390/ijms23126586 - 13 Jun 2022
Cited by 2 | Viewed by 1994
Abstract
The effectiveness of manual therapy in reducing the catabolic effects of performing repetitive intensive force tasks on bones has not been reported. We examined if manual therapy could reduce radial bone microstructural declines in adult female Sprague–Dawley rats performing a 12-week high-repetition and [...] Read more.
The effectiveness of manual therapy in reducing the catabolic effects of performing repetitive intensive force tasks on bones has not been reported. We examined if manual therapy could reduce radial bone microstructural declines in adult female Sprague–Dawley rats performing a 12-week high-repetition and high-force task, with or without simultaneous manual therapy to forelimbs. Additional rats were provided 6 weeks of rest after task cessation, with or without manual therapy. The control rats were untreated or received manual therapy for 12 weeks. The untreated TASK rats showed increased catabolic indices in the radius (decreased trabecular bone volume and numbers, increased osteoclasts in these trabeculae, and mid-diaphyseal cortical bone thinning) and increased serum CTX-1, TNF-α, and muscle macrophages. In contrast, the TASK rats receiving manual therapy showed increased radial bone anabolism (increased trabecular bone volume and osteoblast numbers, decreased osteoclast numbers, and increased mid-diaphyseal total area and periosteal perimeter) and increased serum TNF-α and muscle macrophages. Rest, with or without manual therapy, improved the trabecular thickness and mid-diaphyseal cortical bone attributes but not the mineral density. Thus, preventive manual therapy reduced the net radial bone catabolism by increasing osteogenesis, while rest, with or without manual therapy, was less effective. Full article
(This article belongs to the Special Issue New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration)
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Review

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42 pages, 2739 KiB  
Review
Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids
by Laura Gambari, Antonella Cellamare, Francesco Grassi, Brunella Grigolo, Alessandro Panciera, Alberto Ruffilli, Cesare Faldini and Giovanna Desando
Int. J. Mol. Sci. 2023, 24(11), 9340; https://doi.org/10.3390/ijms24119340 - 26 May 2023
Cited by 4 | Viewed by 2971
Abstract
Obesity (Ob), which has dramatically increased in the last decade, is one of the main risk factors that contribute to the incidence and progression of osteoarthritis (OA). Targeting the characteristics of obesity-associated osteoarthritis (ObOA) may offer new chances for precision medicine strategies in [...] Read more.
Obesity (Ob), which has dramatically increased in the last decade, is one of the main risk factors that contribute to the incidence and progression of osteoarthritis (OA). Targeting the characteristics of obesity-associated osteoarthritis (ObOA) may offer new chances for precision medicine strategies in this patient cohort. First, this review outlines how the medical perspective of ObOA has shifted from a focus on biomechanics to the significant contribution of inflammation, mainly mediated by changes in the adipose tissue metabolism through the release of adipokines and the modification of fatty acid (FA) compositions in joint tissues. Preclinical and clinical studies on n-3 polyunsaturated FAs (PUFAs) are critically reviewed to outline the strengths and weaknesses of n-3 PUFAs’ role in alleviating inflammatory, catabolic and painful processes. Emphasis is placed on potential preventive and therapeutic nutritional strategies based on n-3 PUFAs, with a focus on ObOA patients who could specifically benefit from reformulating the dietary composition of FAs towards a protective phenotype. Finally, tissue engineering approaches that involve the delivery of n-3 PUFAs directly into the joint are explored to address the perspectives and current limitations, such as safety and stability issues, for implementing preventive and therapeutic strategies based on dietary compounds in ObOA patients. Full article
(This article belongs to the Special Issue New Frontiers in Musculoskeletal Tissue Repair and Tissue Regeneration)
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