Matrix metalloproteinase processing of PTHrP yields a selective regulator of osteogenesis, PTHrP

Autor:	J S, Frieling, G, Shay, V, Izumi, S T, Aherne, R G, Saul, M, Budzevich, J, Koomen, C C, Lynch
Rok vydání:	2016
Předmět:	musculoskeletal diseases Osteoblasts Parathyroid Hormone-Related Protein Cell Differentiation musculoskeletal system Matrix Metalloproteinases Article Cell Line Mice Cell Movement Osteogenesis Animals Humans Female Bone Resorption hormones hormone substitutes and hormone antagonists
Zdroj:	Oncogene
ISSN:	1476-5594
Popis:	Parathyroid hormone-related protein (PTHrP) is a critical regulator of bone resorption and augments osteolysis in skeletal malignancies. Here we report that the mature PTHrP(1–36) hormone is processed by matrix metalloproteinases to yield a stable product, PTHrP(1–17). PTHrP(1–17) retains the ability to signal through PTH1R to induce calcium flux and ERK phosphorylation but not cyclic AMP production or CREB phosphorylation. Notably, PTHrP(1–17) promotes osteoblast migration and mineralization in vitro, and systemic administration of PTHrP(1–17) augments ectopic bone formation in vivo. Further, in contrast to PTHrP(1–36), PTHrP(1–17) does not affect osteoclast formation/function in vitro or in vivo. Finally, immunoprecipitation-mass spectrometry analyses using PTHrP(1–17)-specific antibodies establish that PTHrP(1–17) is indeed generated by cancer cells. Thus, matrix metalloproteinase-directed processing of PTHrP disables the osteolytic functions of the mature hormone to promote osteogenesis, indicating important roles for this circuit in bone remodelling in normal and disease contexts.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::66fcd44b5286478f636be2ca80901430 https://pubmed.ncbi.nlm.nih.gov/28368420 Zobrazit plný text záznamu Full text from SpringerLink