PMID- 32079226
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 4
DP  - 2020 Feb 17
TI  - Role of Signal Transduction Pathways and Transcription Factors in Cartilage and 
      Joint Diseases.
LID - 10.3390/ijms21041340 [doi]
LID - 1340
AB  - : Osteoarthritis and rheumatoid arthritis are common cartilage and joint diseases 
      that globally affect more than 200 million and 20 million people, respectively. 
      Several transcription factors have been implicated in the onset and progression 
      of osteoarthritis, including Runx2, C/EBPbeta, HIF2alpha, Sox4, and Sox11. Interleukin-1 
      beta (IL-1beta) leads to osteoarthritis through NF-kB, IkappaBzeta, and the Zn(2+)-ZIP8-MTF1 
      axis. IL-1, IL-6, and tumor necrosis factor alpha (TNFalpha) play a major pathological 
      role in rheumatoid arthritis through NF-kB and JAK/STAT pathways. Indeed, 
      inhibitory reagents for IL-1, IL-6, and TNFalpha provide clinical benefits for 
      rheumatoid arthritis patients. Several growth factors, such as bone morphogenetic 
      protein (BMP), fibroblast growth factor (FGF), parathyroid hormone-related 
      protein (PTHrP), and Indian hedgehog, play roles in regulating chondrocyte 
      proliferation and differentiation. Disruption and excess of these signaling 
      pathways cause genetic disorders in cartilage and skeletal tissues. 
      Fibrodysplasia ossificans progressive, an autosomal genetic disorder 
      characterized by ectopic ossification, is induced by mutant ACVR1. Mechanistic 
      target of rapamycin kinase (mTOR) inhibitors can prevent ectopic ossification 
      induced by ACVR1 mutations. C-type natriuretic peptide is currently the most 
      promising therapy for achondroplasia and related autosomal genetic diseases that 
      manifest severe dwarfism. In these ways, investigation of cartilage and 
      chondrocyte diseases at molecular and cellular levels has enlightened the 
      development of effective therapies. Thus, identification of signaling pathways 
      and transcription factors implicated in these diseases is important.
FAU - Nishimura, Riko
AU  - Nishimura R
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Hata, Kenji
AU  - Hata K
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Takahata, Yoshifumi
AU  - Takahata Y
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Murakami, Tomohiko
AU  - Murakami T
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Nakamura, Eriko
AU  - Nakamura E
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Ohkawa, Maki
AU  - Ohkawa M
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Ruengsinpinya, Lerdluck
AU  - Ruengsinpinya L
AD  - Department of Molecular & Cellular Biochemistry, Osaka University Graduate School 
      of Dentistry1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Cytokines)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (Parathyroid Hormone-Related Protein)
RN  - 0 (RUNX2 protein, human)
RN  - 0 (SOX4 protein, human)
RN  - 0 (SOXC Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (ACVR1 protein, human)
RN  - EC 2.7.11.30 (Activin Receptors, Type I)
SB  - IM
MH  - Achondroplasia/genetics/metabolism
MH  - Activin Receptors, Type I/genetics/metabolism
MH  - Arthritis, Rheumatoid/*genetics/metabolism
MH  - Chondrocytes/metabolism
MH  - Core Binding Factor Alpha 1 Subunit/genetics/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Hedgehog Proteins/genetics/metabolism
MH  - Humans
MH  - Interleukin-1/genetics/metabolism
MH  - MicroRNAs/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Ossification, Heterotopic/genetics/metabolism
MH  - Osteoarthritis/*genetics/metabolism
MH  - Parathyroid Hormone-Related Protein/genetics/metabolism
MH  - Receptor, Fibroblast Growth Factor, Type 3/genetics/metabolism
MH  - SOXC Transcription Factors/*genetics/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Wnt Signaling Pathway/*genetics
PMC - PMC7072930
OTO - NOTNLM
OT  - achondroplasia
OT  - fibrodysplasia ossificans progressive
OT  - osteoarthritis
OT  - rheumatoid arthritis
COIS- The authors declare no conflict of interest.
EDAT- 2020/02/23 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/02/01
CRDT- 2020/02/22 06:00
PHST- 2020/01/17 00:00 [received]
PHST- 2020/02/10 00:00 [revised]
PHST- 2020/02/15 00:00 [accepted]
PHST- 2020/02/22 06:00 [entrez]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - ijms21041340 [pii]
AID - ijms-21-01340 [pii]
AID - 10.3390/ijms21041340 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Feb 17;21(4):1340. doi: 10.3390/ijms21041340.