[Histological function of PTHrP in cartilage].
Parathyroid hormone-related peptide (PTHrP) is known as an important local factor for chondrogenesis, promoting chondrocyte proliferation and inhibiting their differentiation into the hypertrophic phenotype. Signaling transduction through the PTH/PTHrP receptor has two possible pathways: the activation of adenylate cyclase and subsequent protein kinase A (PKA), and the activation of phospholipase C (PLC). Recent studies with mice carrying PTH/PTHrP receptor inactivated for PLC and chondrocyte-specific deletion of the G (s) gene have shown that cAMP/PKA signaling appears to stimulate chondrocyte proliferation and inhibit their differentiation, whereas PLC signaling enhanced chondrocyte differentiation and inhibited their proliferation. In a physiological state, cAMP/PKA signaling may predominate over PLC pathway. Also, Na(+)/H(+)exchanger regulatory factor 2 (NHERF2) has been reported to down-regulate adenylate cyclase activity, in a switch mechanism that results in signal transduction through the PLC pathway.
Li
Minqi
M
Niigata University, Center for Transdisciplinary Research.
Amizuka
Norio
N
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D044162:Parathyroid Hormone-Related Protein; D010750:Phosphoproteins; D044168:Receptor, Parathyroid Hormone, Type 1; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases