L-plastin (LPL) was identified as a potential regulator of the actin-bundling process involved in forming nascent sealing zones (NSZs), which are precursor zones for mature sealing zones. TAT-fused cell-penetrating small molecular weight LPL peptide (TAT- MARGSVSDEE, denoted as an inhibitory LPL peptide) attenuated the formation of NSZs and impaired bone resorption in vitro in osteoclasts. Also, the genetic deletion of LPL in mice demonstrated decreased eroded perimeters and increased trabecular bone density. In the present study, we hypothesized that targeting LPL with the inhibitory LPL peptide in vivo could reduce osteoclast function and increase bone density in a mice model of low bone mass. We injected aging C57BL/6 female mice (36 weeks old) subcutaneously with the inhibitory and scrambled peptides of LPL for 14 weeks. Micro-CT and histomorphometry analyses demonstrated an increase in trabecular bone density of femoral and tibial bones with no change in cortical thickness in mice injected with the inhibitory LPL peptide. A reduction in the serum levels of CTX-1 peptide suggests that the increase in bone density is associated with a decrease in osteoclast function. No changes in bone formation rate and mineral apposition rate, and the serum levels of P1NP indicate that the inhibitory LPL peptide does not affect osteoblast function. Our study shows that the inhibitory LPL peptide can block osteoclast function without impairing the function of osteoblasts. LPL peptide could be developed as a prospective therapeutic agent to treat osteoporosis.

L-塑蛋白（LPL）被认为是参与形成新生密封区（NSZ）的肌动蛋白成束过程的潜在调节剂，新生密封区是成熟密封区的前体区域。 TAT 融合的细胞穿透小分子量 LPL 肽（TAT-MARGSVSDEE，表示为抑制性 LPL 肽）可减弱破骨细胞体外 NSZ 的形成并损害骨吸收。此外，小鼠 LPL 的基因缺失表明侵蚀周长减少，骨小梁密度增加。在本研究中，我们假设体内抑制性 LPL 肽靶向 LPL 可以降低低骨量小鼠模型中的破骨细胞功能并增加骨密度。我们向衰老的 C57BL/6 雌性小鼠（36 周龄）皮下注射 LPL 的抑制肽和乱序肽，持续 14 周。显微 CT 和组织形态计量学分析表明，注射抑制性 LPL 肽的小鼠股骨和胫骨骨小梁密度增加，而皮质厚度没有变化。血清 CTX-1 肽水平的降低表明骨密度的增加与破骨细胞功能的降低有关。骨形成率和矿物质沉积率没有变化，血清P1NP水平表明抑制性LPL肽不影响成骨细胞功能。我们的研究表明，抑制性 LPL 肽可以阻断破骨细胞功能，而不损害成骨细胞的功能。 LPL肽可被开发为治疗骨质疏松症的有前景的治疗剂。