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Effects of targeted overexpression of pleiotrophin on postnatal bone development
Rahul S Tare1, Richard O C Oreffo, Kenzo Sato
1University Orthopaedics, Bone & Joint Research Group, University of Southampton, Southampton, UK.
Insights
Pleiotrophin (PTN) overexpression in mice altered bone growth, enhancing early bone formation but delaying the pubertal growth spurt. This suggests PTN modulates bone development and remodeling processes.
Area of Science:
- Biochemistry
- Developmental Biology
- Orthopedics
Background:
- Pleiotrophin (PTN) is a growth factor associated with extracellular matrix, primarily found in postnatal bone and brain.
- PTN and its receptor, syndecan-3, are synthesized by osteoblasts and present in striated muscle.
Purpose of the Study:
- To investigate the role of PTN in bone development and remodeling using a transgenic mouse model.
- To analyze the effects of PTN overexpression on bone growth, formation, and cartilage integrity from 1 to 30 weeks of age.
Main Methods:
- Generation and analysis of PTN-overexpressing transgenic mice.
- Monitoring bone growth, calcium content, and histological examination of bone and cartilage tissues.
- Localization studies of PTN and its receptor syndecan-3 in various tissues.
Main Results:
- PTN overexpression enhanced intramembranous bone formation and altered long-term bone growth trajectories.
- Transgenic mice exhibited a steady growth pattern without a pubertal growth spurt, reaching similar overall size but with higher bone calcium content by 30 weeks.
- PTN localization in growth plate and articular chondrocytes of transgenics was observed, alongside increased type I collagen synthesis and subchondral bone encroachment into articular cartilage.
Conclusions:
- PTN plays multifaceted roles in in vivo bone formation and remodeling.
- PTN likely acts as a co-factor or accessory protein, modulating the effects of primary signaling molecules in bone development.
Abstract:
Pleiotrophin (PTN) is an extracellular matrix-associated growth/differentiation factor that, in post-natal life, is found mainly in bone and brain. Bone development was investigated in ptn-overexpressing mice between 1 and 30 weeks. In transgenics and controls, PTN (and its receptor syndecan-3) was synthesized by osteoblasts and was present in striated muscle. ptn over-expression enhanced intramembranous bone formation and had multiple effects on long-term bone growth. The pubertal growth spurt did not take place in transgenic mice, in which the growth trajectory was steady and continuous until 25 weeks. By 30 weeks, transgenic and control mice were of the same size, but the calcium content/mg bone was approximately 10% higher in the transgenics. PTN was also localized in growth plate and articular chondrocytes, but only in transgenic mice. In these, synthesis of type I collagen by articular chondrocytes was observed, as well as an encroachment of subchondral bone into the articular cartilage. The results suggest that PTN has multiple roles during in vivo bone formation and remodeling, probably acting as a co-factor or accessory protein that modulates the effects of primary signaling molecules.