Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

Miyatake, Kazumasa; Tsuji, Kunikazu; Yamaga, Mika; Yamada, Jun; Yu, Miao; Abula, Kahaer; Sekiya, Ichiro; Muneta, Takeshi

doi:10.1016/j.bbrc.2012.12.094

Cited by 20 publications

(9 citation statements)

References 32 publications

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“…A recent study in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells showed that YKL-39-activated signal transduction was regulated through the phosphorylation of ERK1/ERK2 kinases (25). YKL-39 was later reported to enhance cell proliferation, colony formation, and type II collagen expression in mouse chondrogenic ATDC5 cells (26). It may therefore act as a novel growth/differentiation factor for articular cartilage chondrocytes, which regulate joint homeostasis in adults.…”

mentioning

confidence: 99%

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

Ranok

Wongsantichon

Robinson

et al. 2015

Journal of Biological Chemistry

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Background: Human YKL-39 is currently recognized as a biomarker for osteoarthritis. Results: Crystal structures of YKL-39 reveal that chitooligosaccharide induces local conformational changes to stabilize sugar⅐protein complexes and that the protein contains five binding subsites for sugars. Conclusion: YKL-39 binds to chitooligosaccharide through enthalpic reactions. Significance: Our findings suggest how YKL-39 interacts with GlcNAc moieties of the natural ligands, which may possibly activate local tissue inflammation.

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mentioning

confidence: 99%

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

Ranok

Wongsantichon

Robinson

et al. 2015

Journal of Biological Chemistry

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“…There is very few information about its roles in insect. In human, CHI3L2 lacks chitinase catalytic activity and is involved in osteoarthritis [50]. This study implies that the member of the chitinase family may contribute to insect immune to invasive fungus in diverse manners.…”

Section: Conidial Survival Under the Chemical And Biochemical Stressesmentioning

confidence: 81%

Transcriptomic analyses reveal comprehensive responses of insect hemocytes to mycopathogen Beauveria bassiana, and fungal virulence-related cell wall protein assists pathogen to evade host cellular defense

et al. 2020

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Entomopathogenic fungi naturally infect insect hosts in environment. Fungal invasion and host immune defense are still in the progress of co-evolution. In this study, entomopathogenic fungus Beauveria bassiana and lepidopteran insect Galleria mellonella were used to investigate host cellular immunity and fungal strategy to evade host defense. First of all, genome-wide expression revealed the transcriptomic responses of hemocytes to insect mycopathogen, which dynamically varied during infection process. Enrichment analysis indicated that differentially expressed genes were primarily involved in metabolism, cellular process and immune system. Notably, cellular response involved a series of hydrolytic enzyme and antimicrobial peptide genes which were sorted together in clustering analysis. In B. bassiana, a cell-wall protein gene (BbCwp) contributes to fungal development in host hemocoel and virulence. RT-qPCR analyses indicated that infection by ΔBbCwp mutant strain caused the up-regulated expression of a series of immunity-related genes, including β-1, 3-glucan recognition protein, hydrolytic enzyme and antimicrobial peptide genes. Disruption of BbCwp resulted in a significant change in conidial lectin-binding feature and the enhanced encapsulation by the host hemocytes. After being treated with hydrolytic enzymes, ΔBbCwp mutant displayed a significantly enhanced sensitivity to osmotic and oxidative stresses. In conclusion, fungal invasion initiates comprehensive physiological responses in the host hemocytes. For mycopathogen, cell-wall protein plays an important role in fungal evasion of immunity defense and colonization in host. Our studies provide an initial framework for exploring more mechanistic details about the fungus-host interaction.

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“…For example, CHI3L2 (also known as YKL-39) has been identified as a biochemical marker for the OA progression in human cartilage since 2002 [ 35 , 36 ]. Functionally, CHI3HL2 has been shown to enhance the proliferation and type II collagen expression in ATDC5 mouse chondrogenic cells [ 37 ]. With the successful generation of polyclonal and monoclonal antibodies against CHI3L2, strong activation of the CHI3L2 was detected not only in human T lymphocyte cell lines and monocytes but in the synovial fluid of an OA patient [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Zheng

2020

IJMS

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Arthritis is the leading cause of disability among adults, while osteoarthritis (OA) is the most common form of arthritis that results in cartilage loss. However, accumulating evidence suggests that the protective hyaline cartilage should not be the sole focus of OA treatment. Particularly, synovium also plays essential roles in OA’s initiation and progression and warrants serious consideration when battling against OA. Thus, biomarkers with similar OA-responsive expressions in cartilage and synovium should be the potential targets for OA treatment. On the other hand, molecules with a distinguished response during OA in cartilage and synovium should be ruled out as OA therapeutic(s) to avoid controversial effects in different tissues. Here, to pave the path for developing a new generation of OA therapeutics, two published transcriptome datasets of knee articular cartilage and synovium were analyzed in-depth. Genes with statistically significantly different expression in OA and healthy cartilage were compared with those in the synovium. Thirty-five genes with similar OA-responsive expression in both tissues were identified while recognizing three genes with opposite OA-responsive alteration trends in cartilage and synovium. These genes were clustered based on the currently available knowledge, and the potential impacts of these clusters in OA were explored.

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Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

Cited by 20 publications

References 32 publications

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

Transcriptomic analyses reveal comprehensive responses of insect hemocytes to mycopathogen Beauveria bassiana, and fungal virulence-related cell wall protein assists pathogen to evade host cellular defense

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

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