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PTH1-34 promotes osteoblast formation through Beclin1-dependent autophagic activation

Haojie Wu 1Ying Xue 1 2Yang Zhang 1 3Yongxuan Wang 1 4Jianming Hou 5 6

J Bone Miner Metab. 2021 Apr 5.doi: 10.1007/s00774-021-01212-7. 


Introduction: PTH1-34 can stimulate osteoblast formation, which contributes to the improvement of bone loss. PTH1-34 can activate autophagy, and autophagy plays a key role in osteoblast formation. This study aimed to explore the role of autophagy in PTH1-34-regulated osteoblastogenesis.

Materials and methods: In this study, the mice treated with ovariectomy (OVX mice) were used to observe the effect of PTH1-34 on the formation and autophagy of osteoblasts in trabecular bone in vivo. Osteoblast precursor cell line MC3T3-E1 was treated with PTH1-34, and then the autophagic parameters of osteoblast precursors (including autophagic proteins and autophagosome formation) were detected using Western Blotting and Transmission Electron Microscopy. Next, after using autophagic pharmacological inhibitor (3-MA) and silencing vectors of autophagic molecule Beclin1 to downregulate autophagic activity, the parameters related to osteogenesis (including ALP staining intensity, ALP activity, cell proliferation and osteoblastic protein expression) were evaluated using corresponding assays.

Results: In vivo results showed that PTH1-34 not only improved bone loss caused by OVX but also restored Beclin1 expression and autophagic activity of immature osteoblasts in bone tissues. In vitro assays also showed that treatment of PTH1-34 enhanced the autophagy in osteoblast precursors. Moreover, under PTH1-34 intervention, the upregulated osteogenic parameters were reversed by autophagic inhibition with 3-MA. Of note, Beclin1 silencing can recover the osteogenic activity enhanced by PTH1-34.

Conclusion: PTH1-34 can enhance the autophagic activity of osteoblast precursors, which is involved in PTH1-34-regulated osteoblast formation. Furthermore, Beclin1, as a key autophagic regulator, plays a pivotal role in PTH1-34-regulated osteoblast precursor autophagy and osteoblastogenesis.