Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13/Integrin α3/RUNX2 feedback loop

Arai, Yoshie; Choi, Bok Hee; Kim, Byoung Ju; Park, Sunghyun; Park, Hyoeun; Moon, James J.; Lee, Soo−Hong

doi:10.1016/j.actbio.2021.02.042

Cited by 32 publications

(19 citation statements)

References 45 publications

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“…During osteogenic differentiation, high expression of MMP13 in hMSCs grew on a type I collagen matrix. Additionally, knocking down MMP13 reduced the osteogenic differentiation of hMSCs on a type I collagen matrix ( Arai et al, 2021 ). TGFB3 is a classic growth factor involved in bone generation ( Yoon et al, 2018 ), and its overexpression upregulates alkaline phosphatase activity and induces the osteogenic differentiation of BMSCs ( He et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA–mRNA Regulatory Networks

Cheng

Zhang

et al. 2021

Front. Genet.

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Background: The clinical efficacy of osteoporosis therapy is unsatisfactory. However, there is currently no gold standard for the treatment of osteoporosis. Recent studies have indicated that a switch from osteogenic to adipogenic differentiation in human bone marrow mesenchymal stem cells (hMSCs) induces osteoporosis. This study aimed to provide a more comprehensive understanding of the biological mechanisms involved in this process and to identify key genes involved in osteogenic and adipogenic differentiation in hMSCs to provide new insights for the prevention and treatment of osteoporosis.Methods: Microarray and bioinformatics approaches were used to identify the differentially expressed genes (DEGs) involved in osteogenic and adipogenic differentiation, and the biological functions and pathways of these genes were analyzed. Hub genes were identified, and the miRNA–mRNA interaction networks of these hub genes were constructed.Results: In an optimized microenvironment, transforming growth factor-beta (TGF-beta) could promote osteogenic differentiation and inhibit adipogenic differentiation of hMSCs. According to our study, 98 upregulated genes involved in osteogenic differentiation and 66 downregulated genes involved in adipogenic differentiation were identified, and associated biological functions and pathways were analyzed. Based on the protein–protein interaction (PPI) networks, the hub genes of the upregulated genes (CTGF, IGF1, BMP2, MMP13, TGFB3, MMP3, and SERPINE1) and the hub genes of the downregulated genes (PPARG, TIMP3, ANXA1, ADAMTS5, AGTR1, CXCL12, and CEBPA) were identified, and statistical analysis revealed significant differences. In addition, 36 miRNAs derived from the upregulated hub genes were screened, as were 17 miRNAs derived from the downregulated hub genes. Hub miRNAs (hsa-miR-27a/b-3p, hsa-miR-128-3p, hsa-miR-1-3p, hsa-miR-98-5p, and hsa-miR-130b-3p) coregulated both osteogenic and adipogenic differentiation factors.Conclusion: The upregulated hub genes identified are potential targets for osteogenic differentiation in hMSCs, whereas the downregulated hub genes are potential targets for adipogenic differentiation. These hub genes and miRNAs play important roles in adipogenesis and osteogenesis of hMSCs. They may be related to the prevention and treatment not only of osteoporosis but also of obesity.

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Section: Discussionmentioning

confidence: 99%

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA–mRNA Regulatory Networks

Cheng

Zhang

et al. 2021

Front. Genet.

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“…On the other hand, ECM remodeling has also been proposed as a novel strategy to control MSCs fate during self-healing, given that the regulation of the expression of matrix metalloproteinases (MMPs), metallopeptidases responsible for the cleavage of the protein components of ECM, may induce MSCs differentiation into osteogenic lineage. For instance, growth of MSCs on a remodeled Col I matrix by MMP13 stimulates osteogenic differentiation and self-healing of bone tissue [ 87 ].…”

Section: Strategies Promoting Bone Healing Through An Endogenous Responsementioning

confidence: 99%

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

Macías

Alcorta-Sevillano

Infante

et al. 2021

IJMS

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Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic (diabetes), genetic (osteogenesis imperfecta), and/or age-related (osteoporosis) etiology, or extrinsic ones coming from external insults such as trauma or surgery. Although bone tissue has an intrinsic capacity of self-repair, large bone defects often require anabolic treatments targeting bone formation process and/or bone grafts, aiming to restore bone loss. The current bone surrogates used for clinical purposes are autologous, allogeneic, or xenogeneic bone grafts, which although effective imply a number of limitations: the need to remove bone from another location in the case of autologous transplants and the possibility of an immune rejection when using allogeneic or xenogeneic grafts. To overcome these limitations, cutting edge therapies for skeletal regeneration of bone defects are currently under extensive research with promising results; such as those boosting endogenous bone regeneration, by the stimulation of host cells, or the ones driven exogenously with scaffolds, biomolecules, and mesenchymal stem cells as key players of bone healing process.

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“…Administration of the factors that induce hypertrophy is not suitable for OA therapy, because this will promote the progression of OA, but it is useful for bone tissue regeneration, by promoting endochondral ossification. For example, it has been reported that the chondrocyte hypertrophy-related gene, MMP13, which is known to lead to the destruction of cartilage tissue, promotes bone regeneration [ 176 ]. In addition, the administration of SPRY4 is inappropriate for OA therapy because it causes chondrocyte hypertrophy, which hinders cartilage regeneration; however, it is appropriate for bone regeneration because chondrocyte hypertrophy is involved in endochondral ossification for bone regeneration [ 177 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis

et al. 2021

Self Cite

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Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte hypertrophy contributes to OA remain elusive. As the pathological processes in the OA cartilage microenvironment, such as the alterations in the extracellular matrix, are initiated and dictated by the physiological state of the chondrocytes, in-depth knowledge of chondrocyte hypertrophy is necessary to enhance our understanding of the disease pathology and develop therapeutic agents. Chondrocyte hypertrophy is a factor that induces OA progression; it is also a crucial factor in the endochondral ossification. This review elaborates on this dual functionality of chondrocyte hypertrophy in OA progression and endochondral ossification through a description of the characteristics of various genes and signaling, their mechanism, and their distinguishable physiological effects. Chondrocyte hypertrophy in OA progression leads to a decrease in chondrogenic genes and destruction of cartilage tissue. However, in endochondral ossification, it represents an intermediate stage at the process of differentiation of chondrocytes into osteogenic cells. In addition, this review describes the current therapeutic strategies and their mechanisms, involving genes, proteins, cytokines, small molecules, three-dimensional environments, or exosomes, against the OA induced by chondrocyte hypertrophy. Finally, this review proposes that the contrasting roles of chondrocyte hypertrophy are essential for both OA progression and endochondral ossification, and that this cellular process may be targeted to develop OA therapeutics.

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Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13/Integrin α3/RUNX2 feedback loop

Cited by 32 publications

References 45 publications

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA–mRNA Regulatory Networks

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA–mRNA Regulatory Networks

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis

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