AI Article Synopsis
- Teriparatide has both bone-building and bone-reducing effects, and a new analog called MY-1 was created that focuses solely on promoting bone formation.
- MY-1 activates specific signaling pathways without triggering others, leading to increased differentiation of bone cells but not affecting the formation of bone-resorbing cells.
- In studies with mice, MY-1 showed potential as a treatment that prevents bone loss and increases bone volume, offering a promising approach for developing osteoporosis therapies without the side effects of bone breakdown.
Article Abstract
Teriparatide (hPTH(1-34)) exhibits both osteoanabolic and osteocatabolic effects. We generated a novel PTH analog by duplicating the PTH(29-34) domain to hPTH(3-34) (named MY-1), which was identified to activate PKC but not PLC and cAMP/PKA signaling. It increased osteo-differentiation but did not affect osteoclastogenesis and RANKL expression in primary osteoblasts or bone marrow cells. MY-1 and hPTH(1-34) increased the synthesis and decreased the degradation οf β-catenin protein in osteoblasts, while PKC inhibitor blunted such effects. In vivo results indicated that intermittent MY-1 and hPTH(1-34) prevented bone loss in ovariectomized mice, and that MY-1 infusion increased bone volume in normal mice. Histological analysis observed more osteoclasts surrounding the cancellous bone surface in hPTH(1-34), but not MY-1 treated mice. We conclude that MY-1 mimicked the osteoanabolic but not the osteocatabolic effects of hPTH(1-34), which is related to PKC and β-catenin signaling. Such anabolic-only analog provides a new strategy to study PTH's versatile functions and design new medicines to treat osteoporosis and bone defects.
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| http://dx.doi.org/10.1016/j.bone.2020.115326 | DOI Listing |
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Article Synopsis
- Teriparatide has both bone-building and bone-reducing effects, and a new analog called MY-1 was created that focuses solely on promoting bone formation.
- MY-1 activates specific signaling pathways without triggering others, leading to increased differentiation of bone cells but not affecting the formation of bone-resorbing cells.
- In studies with mice, MY-1 showed potential as a treatment that prevents bone loss and increases bone volume, offering a promising approach for developing osteoporosis therapies without the side effects of bone breakdown.
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