2017-6-9 Literature Analysis

Oettl et al., Functions of vasopressin and oxytocin in bone mass regulation. Proc Natl Acad Sci U S A , 2016;113(1):164-9, doi: 10.1073/pnas.1523762113., Presented by Tong Li

Questions and Comments:

1Comments: To explore functions of vasopressin and oxytocin in bone mass regulation, the author explored whether Avp and Oxt can share their receptors in the regulation of bone formation by osteoblasts. They find that Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass and Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, showed by Oxtr/ mice have osteopenia, and Avpr1α−/ mice display a high bone mass phenotype, and this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr/:Avpr1α−/ double mutant mice. However, gene expression stimulated by Avp is inhibited when the Oxtr is deleted in Avpr1α−/ cells. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2 does not including in bone formation. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high.

2In the mRNA expression (by qPCR) of osteoblast genes, namely Bglap, Ibsp, Runx2, and Sp7 showed in Fig.1C, why did the curve of the WT and Avpr1α−/ show a trend of recovery after 24 hours?

3In the histomorphometry of spinal trabecular bone from Avpr1α−/, Oxtr/:Avpr1α /, or wild-type mice, expressed as BV/TV shown in Fig.1E, why are the BV/TV values in the two trials so different from those in these two WT groups?

4What happens when Avpr1α moves from the cytoplasm to the nucleus after activation? Does it inhibit reactivation of this receptor?

5Why doesn't oxytocinact on vasopressin receptors?

6Compared with Col2.3Cre:Oxtrfl/fl mice, why does bone formation increase in Col2.3Cre+:Oxtrfl/fl mice ?

7What are the differences in the mechanisms of promoting bone formation between  oxytocin and estrogen ?

8The functions of AVP will be quite different when the concentration of AVP is higher than physiological level. Is the concentration used in the article high or low?

9Why does the author not perform oxytocin stimulation in Oxtr/mice to study whether oxytocin acts on vasopressin receptors?

10How to translate this study into clinical treatment?

2017年06月27日

2017-6-23 Literature Analysis

Oettl et al., Functions of vasopressin and oxytocin in bone mass regulation. Proc Natl Acad Sci U S A , 2016;113(1):164-9, doi: 10.1073/pnas.1523762113. Presented by Tong Li; Edited by Xiaoran Wang

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