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Cellular and Molecular Mechanisms in Bone and Cartilage Damage and...
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Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 5019

Special Issue Editor

Prof. Dr. Philippe Hernigou

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Guest Editor
Orthopaedic Surgery, University Paris East (UPEC), 94010 Creteil, France
Interests: cell therapy; bone union; cartilage regeneration; osteonecrosis

Special Issue Information

Dear Colleagues,

Bones and cartilage, the two most important parts of the musculoskeletal system, provide mobility and maintain the body’s posture. Bone and cartilage damage can have a highly deleterious impact on life and society; therefore, understanding the mechanisms of bone and cartilage regeneration is important. However, questions remain regarding the precise mechanisms of bone formation, how the different molecular processes interact, and the real identity of regenerative cells. 

In this Special Issue, we invite researchers and industry experts to submit their original research articles and reviews related to the following topics and keywords: 

Bone Morphogenic Proteins (BMPs): The role of BMPs in bone and cartilage regeneration; BMP signaling pathways and their implications in orthopedic therapies; and innovative uses of BMPs in reconstructive surgery.

Bone Union with Cell Therapy: Advances in stem cell therapies for fracture non-union; mechanisms and applications of mesenchymal stem cells (MSCs) in bone healing; comparative studies on bone marrow-derived MSCs versus expanded MSCs; and the role of endothelial progenitor cells (EPCs) in bone regeneration.

Cartilage Regeneration: novel cell-based therapies for cartilage repair; functional of collagen/PLA scaffolds in cartilage regeneration; and BMPs in regulating inflammation and promoting osteogenesis at injured growth plates.

Regeneration and Revascularization of Bone Osteonecrosis: Evaluation of bone turnover markers in MSC-regenerative approaches for osteonecrosis; research studies and reviews in bone regeneration for osteonecrosis patients; and evaluation of osteonecrosis regeneration with MRI and histology, and arteriography.

Cartilage Biomarkers: The identification and validation of new cartilage biomarkers; biomarkers in monitoring the progress of cartilage regeneration therapies; and the role of biochemical markers in the diagnosis and treatment of cartilage damage.

Diaphyseal Regeneration with Callostasis: Techniques and outcomes of callostasis in diaphyseal bone regeneration; the use of BMPs and cell-based therapies in enhancing callostasis; and research studies and reviews on the SECCS system and other scaffold-based therapies.

Union with the Membrane Technique: Advances in the membrane technique for guided bone regeneration; mechanisms and applications of barrier membranes in bone healing; and combination therapies involving BMPs and membranes for optimal bone regeneration.

Submissions should provide novel insights, comprehensive reviews, or significant advancements in the field of bone and cartilage damage and regeneration. We hope that a better understanding of the underlying mechanisms can facilitate the development of new strategies for improving bone and cartilage regeneration.

Prof. Dr. Philippe Hernigou
Guest Editor

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. Cells is an international peer-reviewed open access semimonthly 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

  • bone morphogenic proteins (BMPs)
  • bone union with cell therapy
  • advances in stem cell therapies for fracture non-union and cartilage regeneration
  • novel cell-based therapies for cartilage repair
  • functional of collagen/PLA scaffolds in cartilage regeneration
  • regeneration and revascularization of bone osteonecrosis
  • evaluation of osteonecrosis regeneration with MRI and histology, and arteriography
  • identification and validation of new cartilage biomarkers
  • diaphyseal regeneration with callostasis
  • union with the membrane technique

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Published Papers (5 papers)

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Research

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14 pages, 3320 KiB  
Article
TNF-Alpha Inhibitor Prevents Cigarette Smoke Extract-Induced Cell Death in Osteoarthritis-Derived Chondrocytes in Culture
by Débora Levy, Alexandra Fernandes Calllera, Alyne Riani Moreira, Iolanda de Fátima Lopes Calvo Tibério, Pedro Nogueira Giglio, Marco Kawamura Demange, Sergio Paulo Bydlowski and Fernanda Degobbi Tenorio Quirino Dos Santos Lopes
Cells 2025, 14(7), 489; https://doi.org/10.3390/cells14070489 - 25 Mar 2025
Viewed by 437
Abstract
Smoking has been associated, among other factors, with musculoskeletal disorders. Although there is no consensus about the effects of smoking on osteoarthritis (OA), the increase in TNF-alpha in smokers has been considered an important factor in OA induction or progression. However, studies on [...] Read more.
Smoking has been associated, among other factors, with musculoskeletal disorders. Although there is no consensus about the effects of smoking on osteoarthritis (OA), the increase in TNF-alpha in smokers has been considered an important factor in OA induction or progression. However, studies on the effects of smoking on chondrocytes are lacking. Here we aimed to study the effects of cigarette smoke extract (CSE) associated with a TNF-alpha inhibitor on cell death of primary human chondrocytes derived from osteoarthritic patients. CSE at 10% led to cell death by apoptosis after 48 h of incubation, together with caspase 3/7 activation, decrease in mitochondrial transmembrane potential, ROS production, and improvement in syndercan-1, perlecan, and RUNX2 gene expression. All these effects promoted by CSE were reversed by TNF-alpha inhibitor. Collagen II, F-actin, and SOX9 were also analyzed, and CSE promoted alteration in the expression of these proteins. In conclusion, our results support the clinical impact of smoking on OA development by showing the detrimental action of CSE on osteoarthritis-derived chondrocytes and the protective effects of TNF-alpha inhibitors, reinforcing the importance of this cytokine in the cartilage injury process. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration)
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15 pages, 3867 KiB  
Article
Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
by Robert Ossendorff, Sarah Kurth, Su Wang, Max Jaenisch, Elio Assaf, Sebastian Scheidt, Kristian Welle, Christof Burger, Dieter C. Wirtz, Andreas C. Strauss and Frank A. Schildberg
Cells 2025, 14(1), 30; https://doi.org/10.3390/cells14010030 - 31 Dec 2024
Cited by 1 | Viewed by 1065
Abstract
Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. [...] Read more.
Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100–0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration)
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23 pages, 7484 KiB  
Article
Unraveling the Mechanism of Impaired Osteogenic Differentiation in Osteoporosis: Insights from ADRB2 Gene Polymorphism
by Olga Krasnova, Julia Sopova, Anastasiia Kovaleva, Polina Semenova, Anna Zhuk, Daria Smirnova, Daria Perepletchikova, Olga Bystrova, Marina Martynova, Vitaly Karelkin, Olga Lesnyak and Irina Neganova
Cells 2024, 13(24), 2110; https://doi.org/10.3390/cells13242110 - 20 Dec 2024
Viewed by 1041
Abstract
Osteoporosis is characterized by increased resorption and decreased bone formation; it is predominantly influenced by genetic factors. G-protein coupled receptors (GPCRs) play a vital role in bone homeostasis, and mutations in these genes are associated with osteoporosis. This study aimed to investigate the [...] Read more.
Osteoporosis is characterized by increased resorption and decreased bone formation; it is predominantly influenced by genetic factors. G-protein coupled receptors (GPCRs) play a vital role in bone homeostasis, and mutations in these genes are associated with osteoporosis. This study aimed to investigate the impact of single nucleotide polymorphism (SNP) rs1042713 in the ADRB2 gene, encoding the beta-2-adrenergic receptor, on osteoblastogenesis. Herein, using quantitative polymerase chain reaction, western immunoblotting, immunofluorescence assays, and flow cytometry, we examined the expression of ADRB2 and markers of bone matrix synthesis in mesenchymal stem cells (MSCs) derived from osteoporosis patient (OP-MSCs) carrying ADRB2 SNP in comparison with MSCs from healthy donor (HD-MSCs). The results showed significantly reduced ADRB2 expression in OP-MSCs at both the mRNA and protein levels, alongside decreased type 1 collagen expression, a key bone matrix component. Notably, OP-MSCs exhibited increased ERK kinase expression during differentiation, indicating sustained cell cycle progression, unlike that going to HD-MSC. These results provide novel insights into the association of ADRB2 gene polymorphisms with osteogenic differentiation. The preserved proliferative activity of OP-MSCs with rs1042713 in ADRB2 contributes to their inability to undergo effective osteogenic differentiation. This research suggests that targeting genetic factors may offer new therapeutic strategies to mitigate osteoporosis progression. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration)
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14 pages, 3528 KiB  
Article
Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis
by Young-Jin Seo, Jin-Ho Park and June-Ho Byun
Cells 2024, 13(21), 1781; https://doi.org/10.3390/cells13211781 - 28 Oct 2024
Viewed by 1614
Abstract
Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in [...] Read more.
Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration)
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Review

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13 pages, 405 KiB  
Review
The Potential of Red Blood Cells in Regenerative Medicine: A Paradigm Shift in Cellular Therapy
by Fábio Ramos Costa, Joseph Purita, Ansar Mahmood, Rubens Martins, Bruno Costa, Bruno Lima Rodrigues, Stephany Cares Huber, Gabriel Silva Santos, Luyddy Pires, Gabriel Azzini, André Kruel and José Fábio Lana
Cells 2025, 14(11), 797; https://doi.org/10.3390/cells14110797 - 29 May 2025
Abstract
Red blood cells (RBCs) have traditionally been excluded from orthobiologic formulations due to inflammation, oxidative stress, and hemolysis concerns. However, emerging evidence suggests that RBCs may play an active role in regenerative medicine, contributing to immune modulation, vascular support, and oxidative balance. Their [...] Read more.
Red blood cells (RBCs) have traditionally been excluded from orthobiologic formulations due to inflammation, oxidative stress, and hemolysis concerns. However, emerging evidence suggests that RBCs may play an active role in regenerative medicine, contributing to immune modulation, vascular support, and oxidative balance. Their interactions with macrophages, involvement in nitric oxide signaling, and release of extracellular vesicles suggest they may influence tissue repair more than previously assumed. Despite these potential benefits, RBC retention in orthobiologic preparations like platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) remains controversial, with most protocols favoring their removal in the absence of robust translational clinical data. This review explores the biological functions of RBCs in regenerative medicine, their potential contributions to PRP and BMAC, and the challenges associated with their inclusion. While concerns about hemolysis and inflammation persist, controlled studies are needed to determine whether selective RBC retention could enhance musculoskeletal healing in some scenarios. Future research should focus on optimizing RBC processing techniques and evaluating their impact on clinical applications. Addressing these gaps will clarify whether RBCs represent an overlooked but valuable component in regenerative therapies or their exclusion remains justified. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Bone and Cartilage Damage and Regeneration)
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