Peptidomimetic inhibitor of L-plastin reduces osteoclastic bone resorption in aging female mice
Open Access
- 9 April 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Research
- Vol. 9 (1), 1-10
- https://doi.org/10.1038/s41413-020-00135-9
Abstract
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.Keywords
This publication has 75 references indexed in Scilit:
- L-Plastin Regulates Polarization and Migration in Chemokine-Stimulated Human T LymphocytesThe Journal of Immunology, 2012
- Aging and bone loss: new insights for the clinicianTherapeutic Advances in Musculoskeletal Disease, 2011
- The Actin-Bundling Protein L-Plastin: A Critical Regulator of Immune Cell FunctionInternational Journal of Cell Biology, 2011
- Denosumab for the Prevention of Osteoporotic Fractures in Post-Menopausal WomenPharmacoEconomics, 2011
- Regulation of Sealing Ring Formation by L-plastin and Cortactin in Osteoclasts*Online Journal of Public Health Informatics, 2010
- Age-Related Changes in Bone Structure and Strength in Female and Male BALB/c MiceCalcified Tissue International, 2010
- Estrogen and bone: Insights from estrogen-resistant, aromatase-deficient, and normal menBone, 2008
- A Population-Based Assessment of Rates of Bone Loss at Multiple Skeletal Sites: Evidence for Substantial Trabecular Bone Loss in Young Adult Women and MenJournal of Bone and Mineral Research, 2008
- Skeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex SteroidsOnline Journal of Public Health Informatics, 2007
- Rosiglitazone Induces Decreases in Bone Mass and Strength that Are Reminiscent of Aged BoneEndocrinology, 2007