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PTHrP in the periosteum regulates long bone growth
DOI:10.1038/bonekey.2014.124
Wang et al. used transgenic mice with a conditional deletion of the gene encoding parathyroid hormone-related peptide (PTHrP) in the fibrous layer of the periosteum to understand more about the regulation of linear growth at long bone surfaces. The deletion was achieved using scleraxis gene targeting.
Bone modeling within the lateral tibial metaphysis and metaphyseal–diaphyseal junction (MDJ) was abnormal, with the formation of a protruding instead of concave metaphysis. The gene knockout also resulted in a 75% reduction in the number of osteoclasts present at the cortical surface due to interruption of RANKL receptor activator induction.
In the fibulae of the knockout mice, the metaphysis was abnormally shaped, resembling a club and the entire bone formed with a different 3D profile compared to wild type. The periosteal circumference at the mid-diaphysis and the MDJ was up to 45% larger (P≤0.001 for both).
The authors conclude that PRHrP within the periosteum regulates bone modeling in the MDJ during growth of long bones and, in the fibula, determines the overall shape of the bone.
Editor’s comment: Perhaps the most interesting result in this study is the targeted deletion of a gene (PTHrP) in the periosteum using the scleraxis promoter. There are so few studies that have specifically examined the role of periosteally expressed factors so far. This study may encourage more research in this specific area.
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