RGD Reference Report - Heat shock protein 60 protects skeletal tissue against glucocorticoid-induced bone mass loss by regulating osteoblast survival. - Rat Genome Database

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Heat shock protein 60 protects skeletal tissue against glucocorticoid-induced bone mass loss by regulating osteoblast survival.

Authors: Wang, FS  Wu, RW  Ko, JY  Tai, MH  Ke, HC  Yeh, DW  Wu, SL  Chen, MW 
Citation: Wang FS, etal., Bone. 2011 Nov;49(5):1080-9. doi: 10.1016/j.bone.2011.08.006. Epub 2011 Aug 11.
RGD ID: 10402841
Pubmed: PMID:21854881   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bone.2011.08.006   (Journal Full-text)

Excessive glucocorticoid administration accelerates osteoblast apoptosis and skeletal deterioration. Heat shock proteins (HSPs) regulate metabolic activities in osteoblastic cells. This study characterized the biological significance of HSP60 in glucocorticoid-induced bone loss. Rats were treated with glucocorticoid, HSP60 antisense oligonucleotides, or adenovirus-mediated HSP60 gene transfer. Bone mineral density, metaphyseal trabecular micro-architecture, and fragility were analyzed by dual X-ray absorptiometry, micro-computed tomography, and material testing, respectively. Differential proteomic profiles of bone tissue extracts were detected by bi-dimensional electrophoresis and mass spectrometry. Survival and proapoptotic signal transduction were quantified by immunoblotting. Glucocorticoid-treated rats had low bone mineral density and metaphyseal trabecular microstructure in association with downregulation of collagen 1alpha1 and HSP60 expressions in bone tissue. Gain of HSP60 function by adenovirus-mediated HSP60 gene transfer abrogated the deleterious effects of glucocorticoid treatment on bone mass, trabecular microstructure, and mechanical strength. Enhancement of HSP60 signaling attenuated the glucocorticoid-induced loss of trabecular bone volume, mineral acquisition reactions and osteoblast surface. HSP60 gene transfer activated ERK and Akt and reduced Bax and cytochrome c release, as well as caspase-3 cleavage, which attenuated the inhibitory effects of glucocorticoid treatment on osteoblast survival. Loss of HSP60 function by HSP60 antisense oligonucleotides accelerated mitochondrial apoptotic programs and osteoblast apoptosis. Knockdown of HSP60 induced loss of bone mass, micro-architecture integrity, and mechanical property. Taken together, loss of HSP60 signaling contributes to the glucocorticoid-induced enhancement of pro-apoptotic reactions, thereby accelerating osteoblast apoptosis and bone mass loss. Enhancement of HSP60 function is beneficial for protecting bone tissue against the glucocorticoid-induced inhibition of bone cell viability and bone formation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hspd1Ratapoptotic mitochondrial changes  IMP  RGD 
Hspd1Ratnegative regulation of apoptotic process in bone marrow cell  IMP  RGD 
Hspd1Ratresponse to glucocorticoid  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspd1  (heat shock protein family D (Hsp60) member 1)


Additional Information