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Inhibition of protein kinase-D promotes cartilage repair at injured growth plate in rats

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dc.contributor.authorChung, R.
dc.contributor.authorFoster, B.
dc.contributor.authorXian, C.
dc.date.issued2013
dc.description.abstractIntroduction: Injured growth plate cartilage is often repaired by bony tissue, causing bone growth defects in children. Currently, mechanisms for the undesirable repair remain unclear and there are no biological treatments available to prevent the associated bone growth defects. Osterix is known as a vital transcription factor for osteoblast differentiation which is critical for normal bone formation and bone repair, and osterix is known to be regulated by protein kinase-D; however it is unknown whether protein kinase-D–osterix signalling plays any roles in the bony repair of injured growth plate. Methods: Using a rat model, this study investigated potential roles of protein kinase-D (PKD) in regulating expression of osteogenic transcription factor osterix and the growth plate bony repair. 4 days post injury at the proximal tibial growth plate, rats received four once-daily injections of vehicle or 2.35 mg/kg go¨6976 (a PKD inhibitor), and growth plate tissues collected at day 10 were examined histologically and molecularly. In addition, effects of PKD inhibition on osteogenic and chondrogenic differentiation were examined in vitro using rat bone marrow mesenchymal stromal cells. Results: Compared to vehicle control, PKD inhibition caused a decrease in bone volume (p < 0.05), an increase in % of mesenchymal tissue (p < 0.01), and an increase in cartilaginous tissue within the injury site. Consistently, go¨6976 treatment tended to decrease expression of bone-related genes (osterix, osteocalcin) and increase levels of cartilage-related genes (Sox9, collagen-2a, collagen-10a1). In support, in vitro experiments showed that go¨6976 presence in the primary rat marrow stromal cell culture resulted in a decrease of alkaline phosphatase+ CFU-f colonies formed (p < 0.05) and an increase in collagen-2a expression in chondrogenic pellet culture (p < 0.05). Conclusion: These studies suggest that PKD is important for growth plate bony repair and its inhibition after growth plate injury may result in less bone formation and potentially more cartilage repair.
dc.description.statementofresponsibilityRosa Chung, Bruce K. Foster and Cory J. Xian
dc.identifier.citationInjury, 2013; 44(7):914-922
dc.identifier.doi10.1016/j.injury.2013.01.038
dc.identifier.issn0020-1383
dc.identifier.issn1879-0267
dc.identifier.orcidXian, C. [0000-0002-8467-2845]
dc.identifier.urihttp://hdl.handle.net/2440/79408
dc.language.isoen
dc.publisherElsevier Sci Ltd
dc.relation.grantNHMRC
dc.rights© 2013 Elsevier Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.injury.2013.01.038
dc.subjectdifferentiation
dc.subjectgrowth plate
dc.subjectinjury repair
dc.subjectosteoblasts
dc.subjectosterix
dc.subjectprotein kinase-D
dc.subjectstromal progenitor cells
dc.titleInhibition of protein kinase-D promotes cartilage repair at injured growth plate in rats
dc.typeJournal article
pubs.publication-statusPublished

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