ESPE Abstracts (2014) 82 P-D-1-1-135

The Association Between Adipocytes and Growth is Mediated by Growth and Differentiation Factor 5

Biana Shtaifa,b, Nitzan Drorc, Meytal Bar-Maiselsa,c, Moshe Phillipb,c & Galia Gat-Yablonskia,c

aFelsentein Medical Research Center, Petah Tikva, Israel; bSackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel; cSchneider Children’s Medical Center of Israel, Petah Tikva, Israel

Background: The association between nutrition and growth is common knowledge but the mechanism is still unelucidated. Several reported cases in the literature describe growth without GH, that in most cases were associated with obesity, suggesting, that the adipocytes might have a role in regulating linear growth.

Objective and hypotheses: The aim of the study was to search for a skeletal growth factor that is secreted by adipocytes.

Method: 3T3L1 cells were induced to differentiate into adipocytes and their conditioned medium (CM) was added to metatarsals bone culture. Studying the differentially expressed growth factors identified growth and differentiation factor 5 (GDF5) as a possible mediator.

Results: CM of adipocytes significantly increased metatarsals bone elongation. GDF5 was found to be expressed 700 fold higher by adipocytes compared to non differentiated cells and to be secreted into their CM. The presence of BMPR1 on metatarsal bone was confirmed. GDF5 significantly increased metatarsal length in culture.

Conclusion: In this study we showed that CM of the 3T3L1 adipocytes directly stimulates growth of metatarsal bones in culture. Specifically we found that GDF5, a growth factor that plays an important role in limb mesenchymal cell condensation and chondrogenesis is a possible mediator of this stimulation. These results add a new understanding of the interaction between nutrition and growth.

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