Molecular and Cellular Mechanisms of Bone and Cartilage Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 13430

Special Issue Editor


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Guest Editor
Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
Interests: interaction between the skeletal and immune systems in health and diseases; bone and cartilage metabolism
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Special Issue Information

Dear Colleagues,

Bones and cartilage form the most important parts of the musculoskeletal system that provides mobility and maintains body posture. Musculoskeletal disorders, namely, those affecting bone and cartilage, limit the mobility and productivity of individuals, leading to early retirement from work and a reduced ability of people to participate in society. Osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain are the major musculoskeletal disorders and represent a significant socioeconomic burden on individuals and medical services worldwide. A better understanding of the pathophysiology of bone and cartilage in these diseases should provide important clues for the discovery of new therapies. The current Special Issue focuses on molecular and cellular mechanisms underlining bone and cartilage pathology and novel therapeutic approaches targeting the above diseases. We welcome research or review articles focusing on the following topics:

  1. Molecular and cellular mechanisms underlining bone and cartilage pathology in related diseases;
  2. Bone and cartilage metabolism in health and disease;
  3. Therapeutic strategies for prevention of bone and cartilage pathology;
  4. Novel approaches for bone and cartilage regeneration.

Dr. M. Alaa Terkawi
Guest Editor

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Keywords

  • pathophysiology of bone and cartilage
  • therapy
  • osteoarthritis
  • rheumatoid arthritis
  • osteoporosis
  • low back pain

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Published Papers (7 papers)

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Editorial

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2 pages, 176 KiB  
Editorial
Molecular and Cellular Mechanisms of Bone and Cartilage Diseases
by M. Alaa Terkawi
Biomedicines 2023, 11(9), 2492; https://doi.org/10.3390/biomedicines11092492 - 08 Sep 2023
Viewed by 462
Abstract
Bones and cartilage, the two most important parts of the musculoskeletal system, provide mobility and maintain the body’s posture [...] Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)

Research

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10 pages, 1557 KiB  
Communication
Development of an Animal Model for Traumatic Brain Injury Augmentation of Heterotopic Ossification in Response to Local Injury
by Chandrasekhar Kesavan, Gustavo A. Gomez, Sheila Pourteymoor and Subburaman Mohan
Biomedicines 2023, 11(3), 943; https://doi.org/10.3390/biomedicines11030943 - 18 Mar 2023
Cited by 3 | Viewed by 1399
Abstract
Heterotopic ossification (HO) is the abnormal growth of bone in soft connective tissues that occurs as a frequent complication in individuals with traumatic brain injury (TBI) and in rare genetic disorders. Therefore, understanding the mechanisms behind ectopic bone formation in response to TBI [...] Read more.
Heterotopic ossification (HO) is the abnormal growth of bone in soft connective tissues that occurs as a frequent complication in individuals with traumatic brain injury (TBI) and in rare genetic disorders. Therefore, understanding the mechanisms behind ectopic bone formation in response to TBI is likely to have a significant impact on identification of novel therapeutic targets for HO treatment. In this study, we induced repetitive mild TBI (mTBI) using a weight drop model in mice and then stimulated HO formation via a local injury to the Achilles tendon or fibula. The amount of ectopic bone, as evaluated by micro-CT analyses, was increased by four-fold in the injured leg of mTBI mice compared to control mice. However, there was no evidence of HO formation in the uninjured leg of mTBI mice. Since tissue injury leads to the activation of hypoxia signaling, which is known to promote endochondral ossification, we evaluated the effect of IOX2, a chemical inhibitor of PHD2 and a known inducer of hypoxia signaling on HO development in response to fibular injury. IOX2 treatment increased HO volume by five-fold compared to vehicle. Since pericytes located in the endothelium of microvascular capillaries are known to function as multipotent tissue-resident progenitors, we determined if activation of hypoxia signaling promotes pericyte recruitment at the injury site. We found that markers of pericytes, NG2 and PDGFRβ, were abundantly expressed at the site of injury in IOX2 treated mice. Treatment of pericytes with IOX2 for 72 h stimulated expression of targets of hypoxia signaling (Vegf and Epo), as well as markers of chondrocyte differentiation (Col2α1 and Col10α1). Furthermore, serum collected from TBI mice was more effective in promoting the proliferation and differentiation of pericytes than control mouse serum. In conclusion, our data show that the hypoxic state at the injury site in soft tissues of TBI mice provides an environment leading to increased accumulation and activation of pericytes to form endochondral bone. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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11 pages, 1724 KiB  
Article
In Vitro Evaluation of the Effects of Hyaluronic Acid and an Aminoacidic Pool on Human Osteoblasts
by Maria Addolorata Bonifacio, Amalia Cassano, Alessandra Vincenti, Angela Vinella, Fabio Dell’Olio, Gianfranco Favia and Maria Addolorata Mariggiò
Biomedicines 2023, 11(3), 751; https://doi.org/10.3390/biomedicines11030751 - 01 Mar 2023
Cited by 3 | Viewed by 1156
Abstract
The treatment of bone injuries must be timely and effective to improve the chances of full recovery. In this respect, a mix of hyaluronic acid and an amino acidic pool has been marketed to promote soft tissue healing, fastening recovery times. Several studies [...] Read more.
The treatment of bone injuries must be timely and effective to improve the chances of full recovery. In this respect, a mix of hyaluronic acid and an amino acidic pool has been marketed to promote soft tissue healing, fastening recovery times. Several studies have reported the in vitro and in vivo influence of hyaluronic acid and amino acids on fibroblasts and keratinocytes, highlighting the enhancement of cell proliferation, motility and cytokines synthesis. Even though the effectiveness of this combination of molecules on bone repair has been described in vivo, to the best of our knowledge, its in vitro effects on osteoblasts still need to be investigated. Therefore, this work describes for the first time osteoblast metabolism, proliferation and in vitro differentiation in the presence of hyaluronic acid and amino acids, aiming at understanding the mechanisms underlying their effectiveness in injured tissue repair. The reported results demonstrate the enhancement of osteoblasts’ metabolic activity and the fastening of cell cycle progression. Furthermore, gene expression studies show a significant increase in differentiation markers, i.e., osteoprotegerin and osteonectin. Finally, alkaline phosphatase activity is also boosted by the combination of hyaluronic acid and aminoacids, confirming the ability of in vitro cultured cells to properly differentiate through the osteogenic lineage. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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10 pages, 678 KiB  
Article
Arginine Availability in Reamed Intramedullary Aspirate as Predictor of Outcome in Nonunion Healing
by Dennis M. Meesters, Karolina A. P. Wijnands, Hans M. H. van Eijk, Martijn Hofman, Frank Hildebrand, Jan P. A. M. Verbruggen, Peter R. G. Brink and Martijn Poeze
Biomedicines 2022, 10(10), 2474; https://doi.org/10.3390/biomedicines10102474 - 03 Oct 2022
Cited by 1 | Viewed by 1073
Abstract
Fracture healing and nonunion development are influenced by a range of biological factors. Adequate amino acid concentrations, especially arginine, are known to be important during normal bone healing. We hypothesize that bone arginine availability in autologous bone marrow grafting, when using the reamer-irrigator-aspirator [...] Read more.
Fracture healing and nonunion development are influenced by a range of biological factors. Adequate amino acid concentrations, especially arginine, are known to be important during normal bone healing. We hypothesize that bone arginine availability in autologous bone marrow grafting, when using the reamer-irrigator-aspirator (RIA) procedure, is a marker of bone healing capacity in patients treated for nonunion. Seventeen patients treated for atrophic long bone nonunion by autologous bone grafting by the RIA procedure were included and divided into two groups, successful treatment of nonunion and unsuccessful, and were compared with control patients after normal fracture healing. Reamed bone marrow aspirate from a site distant to the nonunion was obtained and the amino acids and enzymes relevant to arginine metabolism were measured. Arginine and ornithine concentrations were higher in patients with successful bone healing after RIA in comparison with unsuccessful healing. Ornithine concentrations and arginase-1 expression were lower in all nonunion patients compared to control patients, while citrulline concentrations were increased. Nitric oxide synthase 2 (Nos2) expression was significantly increased in all RIA-treated patients, and higher in patients with a successful outcome when compared with an unsuccessful outcome. The results indicate an influence of the arginine–nitric oxide metabolism in collected bone marrow, on the outcome of nonunion treatment, with indications for a prolonged inflammatory response in patients with unsuccessful bone grafting therapy. The determination of arginine concentrations and Nos2 expression could be used as a predictor for the successful treatment of autologous bone grafting in nonunion treatment. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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11 pages, 624 KiB  
Article
The Impact of an Adapted Physical Activity Program on Bone Turnover, Physical Performance and Fear of Falling in Osteoporotic Women with Vertebral Fractures: A Quasi-Experimental Pilot Study
by Francesca Maffei, Alice Masini, Sofia Marini, Angela Buffa, Nazzarena Malavolta, Pasqualino Maietta Latessa and Laura Dallolio
Biomedicines 2022, 10(10), 2467; https://doi.org/10.3390/biomedicines10102467 - 02 Oct 2022
Cited by 3 | Viewed by 1481
Abstract
Physical activity has been indicated as a potential strategy to counteract osteoporosis (OP). This study of post-menopausal women with osteoporotic vertebral fractures investigated the effect of an adapted physical activity (APA) program on two serum bone turnover biomarkers (Bone Alkaline Phosphatase, B-ALP and [...] Read more.
Physical activity has been indicated as a potential strategy to counteract osteoporosis (OP). This study of post-menopausal women with osteoporotic vertebral fractures investigated the effect of an adapted physical activity (APA) program on two serum bone turnover biomarkers (Bone Alkaline Phosphatase, B-ALP and C-terminal telopeptide of type 1 collagen, CTX-1), functional capacity (6-Minutes Walking Test, 6MWT), and risk and fear of falls (Tinetti and Falls Efficacy scale). The APA group (n = 12) performed a 1-h group session twice per week for 6 months whereas the control group (n = 9) was asked to maintain their current lifestyle. The exercise program did not affect the serum concentrations of B-ALP and CTX-1 biomarkers measured at the baseline and after 6 months in women of the APA group. Moreover, at the end of intervention no significant differences in serum concentrations for either biomarker was observed between the two study groups. Interestingly, when compared to the control group, women in the APA group showed significant improvement in the functional capacity measures by 6MWT (p = 0.037) and a decrease of the risk and fear of falls as indicated by the Tinetti test (p = 0.043). Based on these findings, exercise could provide new perspectives for the care and management of OP. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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16 pages, 1783 KiB  
Article
Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes
by Annett Eitner, Simon Sparing, Felix C. Kohler, Sylvia Müller, Gunther O. Hofmann, Thomas Kamradt, Hans-Georg Schaible and Matthias Aurich
Biomedicines 2022, 10(6), 1349; https://doi.org/10.3390/biomedicines10061349 - 08 Jun 2022
Cited by 7 | Viewed by 1851
Abstract
Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were [...] Read more.
Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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Review

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18 pages, 1394 KiB  
Review
Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention
by M Alaa Terkawi, Taku Ebata, Shunichi Yokota, Daisuke Takahashi, Tsutomu Endo, Gen Matsumae, Tomohiro Shimizu, Ken Kadoya and Norimasa Iwasaki
Biomedicines 2022, 10(5), 1109; https://doi.org/10.3390/biomedicines10051109 - 10 May 2022
Cited by 21 | Viewed by 5029
Abstract
Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, [...] Read more.
Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Bone and Cartilage Diseases)
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