RGD Reference Report - Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis. - Rat Genome Database

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Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis.

Authors: Buckbinder, L  Crawford, DT  Qi, H  Ke, HZ  Olson, LM  Long, KR  Bonnette, PC  Baumann, AP  Hambor, JE  Grasser WA, 3RD  Pan, LC  Owen, TA  Luzzio, MJ  Hulford, CA  Gebhard, DF  Paralkar, VM  Simmons, HA  Kath, JC  Roberts, WG  Smock, SL  Guzman-Perez, A  Brown, TA  Li, M 
Citation: Buckbinder L, etal., Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10619-24. Epub 2007 May 30.
RGD ID: 1642610
Pubmed: PMID:17537919   (View Abstract at PubMed)
PMCID: PMC1880863   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0701421104   (Journal Full-text)

Bone is accrued and maintained primarily through the coupled actions of bone-forming osteoblasts and bone-resorbing osteoclasts. Cumulative in vitro studies indicated that proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of osteoclast function and activity. However, our investigation of PYK2-/- mice did not reveal evidence supporting an essential function for PYK2 in osteoclasts either in vivo or in culture. We find that PYK2-/- mice have high bone mass resulting from an unexpected increase in bone formation. Consistent with the in vivo findings, mouse bone marrow cultures show that PYK2 deficiency enhances differentiation and activity of osteoprogenitor cells, as does expressing a PYK2-specific short hairpin RNA or dominantly interfering proteins in human mesenchymal stem cells. Furthermore, the daily administration of a small-molecule PYK2 inhibitor increases bone formation and protects against bone loss in ovariectomized rats, an established preclinical model of postmenopausal osteoporosis. In summary, we find that PYK2 regulates the differentiation of early osteoprogenitor cells across species and that inhibitors of the PYK2 have potential as a bone anabolic approach for the treatment of osteoporosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTK2BHumanPostmenopausal Osteoporosis  ISOPtk2b (Rattus norvegicus) RGD 
Ptk2bRatPostmenopausal Osteoporosis  IMP  RGD 
Ptk2bMousePostmenopausal Osteoporosis  ISOPtk2b (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptk2bRatnegative regulation of ossification  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptk2b  (protein tyrosine kinase 2 beta)

Genes (Mus musculus)
Ptk2b  (PTK2 protein tyrosine kinase 2 beta)

Genes (Homo sapiens)
PTK2B  (protein tyrosine kinase 2 beta)


Additional Information