Endochondral ossification (Homo sapiens)
From WikiPathways
Description
Thyroid hormone and especially triiodothyronine induce morphological hypertrophy of chondrocytes, through binding to thyroid hormone receptors. Further, triiodothyronine increases the total collagen production in chondrocytes, as also terminal differentiation, but triiodothyronine also induces cell death through non-apoptotic modes of physiological death. Triiodothyronine acts by altering intracellular gene expression after receptor binding, and is crucial for growth, as receptor deficiencies lead to dwarfism and growth retardation. Thyroid hormone inhibits the PTHR1 gene, which encodes for a g-protein coupled receptor for parathyroid hormone (PTH) and PTH-like hormones. PTH receptors activate adenylyl cyclase and a phosphatidylinositol-calcium second messenger system. They control the levels of calcium in the blood and thus, ossification as they inhibit hypertrophy upon activation (Mackie, Randau, https://rarediseases.org/rare-diseases/jansen-type-metaphyseal-chondrodysplasia/ ). Oxygen acts upon RUNX2 and HDAC4 in the ossification process. HDAC4 is a class II histone deacetylase/acuc/apha family gene, and if tethered to a promoter, it represses transcription (https://www.ncbi.nlm.nih.gov/gene/9759). Via this mechanism, HDAC4 represses RUNX2 in the ossification process. RUNX2 is a member of the RUNX family of transcription factors, encoding a nuclear protein with an RUND DNA-binding domain. It induces osteoblastic differentiation and skeletal morphogenesis, as it acts upon the DNA and regulatory factors (https://www.ncbi.nlm.nih.gov/gene/860). Thus, RUNX2 acts directly upon chondrocytical hypertrophy. Cyclic adenosine monophosphate (cAMP) act upon protein kinase A (PKA), which phosphorylates proteins if activated. In this case it leads to the inhibition of Sox9 (https://www.nature.com/articles/nm.3314). Sox9 induces cell proliferation and inhibits hypertrophy and is regulating the transcription of the anti-müllerian hormone.
Proteins on this pathway have targeted assays available via the CPTAC Assay PortalQuality Tags
Ontology Terms
Bibliography
- Belluoccio D, Bernardo BC, Rowley L, Bateman JF; ''A microarray approach for comparative expression profiling of the discrete maturation zones of mouse growth plate cartilage.''; Biochim Biophys Acta, 2008 PubMed Europe PMC Scholia
- Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M; ''Endochondral ossification: how cartilage is converted into bone in the developing skeleton.''; Int J Biochem Cell Biol, 2008 PubMed Europe PMC Scholia
- Randau TM, Schildberg FA, Alini M, Wimmer MD, Haddouti el-M, Gravius S, Ito K, Stoddart MJ; ''The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.''; PLoS One, 2013 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ADAMTS1 | GeneProduct | 9510 (Entrez Gene) | |
ADAMTS4 | GeneProduct | 9507 (Entrez Gene) | |
ADAMTS5 | GeneProduct | 11096 (Entrez Gene) | |
AKP2 | GeneProduct | 249 (Entrez Gene) | |
AKT | GeneProduct | 207 (Entrez Gene) | |
Adseverin | GeneProduct | 85477 (Entrez Gene) | PMID: 17097081 |
Aggrecan | GeneProduct | 176 (Entrez Gene) | |
BMP6 | GeneProduct | 654 (Entrez Gene) | |
BMP7 | GeneProduct | 655 (Entrez Gene) | |
BMPR1A | GeneProduct | 657 (Entrez Gene) | |
Bapx1 | GeneProduct | 579 (Entrez Gene) | |
C4ST1 | GeneProduct | 50515 (Entrez Gene) | |
CAB39 | GeneProduct | 51719 (Entrez Gene) | |
CALM1 | GeneProduct | 801 (Entrez Gene) | |
CDKN1C | GeneProduct | 1028 (Entrez Gene) | |
COL10A1 | GeneProduct | 1300 (Entrez Gene) | |
COL2A1 | GeneProduct | 1280 (Entrez Gene) | |
Carminerin | GeneProduct | 1473 (Entrez Gene) |
|
Cathepsin L2 | GeneProduct | 1515 (Entrez Gene) | Taken as homologue to mouse Cathepsin L (Ctsl) |
DDR2 | GeneProduct | 4921 (Entrez Gene) | |
FGF18 | GeneProduct | 8817 (Entrez Gene) | |
FGF2 | GeneProduct | 2247 (Entrez Gene) | |
FGFR1 | GeneProduct | 2260 (Entrez Gene) | |
FGFR3 | GeneProduct | 2261 (Entrez Gene) | |
FrzB-1 | GeneProduct | 2487 (Entrez Gene) | |
GH receptor | GeneProduct | 2690 (Entrez Gene) | |
GLI3 | GeneProduct | 2737 (Entrez Gene) | |
Growth hormone | GeneProduct | 2688 (Entrez Gene) | |
HDAC4 | GeneProduct | 9759 (Entrez Gene) | |
HMGCS1 | GeneProduct | 3157 (Entrez Gene) | |
IGF1 | GeneProduct | 3479 (Entrez Gene) | |
IGF1R | GeneProduct | 3480 (Entrez Gene) | |
IGF2 | GeneProduct | 3481 (Entrez Gene) | |
IHH | GeneProduct | 3549 (Entrez Gene) | |
KIF3A | GeneProduct | 11127 (Entrez Gene) | |
MEF2C | GeneProduct | 4208 (Entrez Gene) | |
MGP | GeneProduct | 4256 (Entrez Gene) | |
MMP13 | GeneProduct | 4322 (Entrez Gene) | |
MMP9 | GeneProduct | 4318 (Entrez Gene) | |
NPP1 | GeneProduct | 5167 (Entrez Gene) | |
Osteopontin | GeneProduct | 6696 (Entrez Gene) | |
Oxygen | Metabolite | HMDB0001377 (HMDB) | |
PKA | GeneProduct | 5566 (Entrez Gene) | |
PLAT | GeneProduct | 5327 (Entrez Gene) | |
PLAU | GeneProduct | 5328 (Entrez Gene) | |
PTCH1 | GeneProduct | 5727 (Entrez Gene) | |
PTCH | GeneProduct | 5727 (Entrez Gene) | |
PTH | GeneProduct | 5741 (Entrez Gene) | |
PTHR1 | GeneProduct | 5745 (Entrez Gene) | |
PTHrP | GeneProduct | 5744 (Entrez Gene) | |
RUNX2 | GeneProduct | 860 (Entrez Gene) | |
RUNX3 | GeneProduct | 864 (Entrez Gene) | |
SERPINH1 | GeneProduct | 871 (Entrez Gene) | |
SLC38A2 | GeneProduct | 54407 (Entrez Gene) | |
SOX5 | GeneProduct | 6660 (Entrez Gene) | |
SOX6 | GeneProduct | 55553 (Entrez Gene) | |
STAT1 | GeneProduct | 6772 (Entrez Gene) | |
STAT5 | GeneProduct | 6777 (Entrez Gene) | |
Sox9 | GeneProduct | 6662 (Entrez Gene) | |
TG737 | GeneProduct | 8100 (Entrez Gene) | |
TGFB1 | GeneProduct | 7040 (Entrez Gene) | |
TGFB2 | GeneProduct | 7042 (Entrez Gene) | |
TGFBI | GeneProduct | 7040 (Entrez Gene) | |
THRA | GeneProduct | 7067 (Entrez Gene) | |
TIMP3 | GeneProduct | 7078 (Entrez Gene) | |
TNAP | GeneProduct | 445341 (Entrez Gene) | |
Thyroid hormone | Metabolite | CHEBI:60311 (ChEBI) | |
Triiodothyronine | Metabolite | CHEBI:24864 (ChEBI) | |
VEGFA | GeneProduct | 7422 (Entrez Gene) | |
cAMP | Metabolite | HMDB0000058 (HMDB) |
Annotated Interactions
No annotated interactions