Parathyroid hormone (PTH) related peptide (PTHrP) is thought to influence the proliferation and differentiation of the epidermis and hair follicle. As a means of elucidating the biologic function of PTHrP on the hair follicle, a PTHrP analog PTH (7-34), which is a PTH/PTHrP receptor antagonist, was given intraperitoneally twice daily to C57 BL/6 mice at different stages of the hair cycle. PTH (7-34) induced 99 +/- 4.5% (mean +/- SEM) of resting telogen hair follicles into a proliferative (anagen) state, whereas 100% of the hair follicles in the control group remained in telogen. To determine whether this peptide influenced the progression of the hair follicles from anagen to catagen (hair follicle maturation and regression), groups of mice that were either spontaneously in or induced to anagen received either PTH (7-34) or placebo. Morphometric analysis of the hair follicles from the middle back region of the spontaneous anagen mice that received PTH (7-34) revealed that 19 +/- 4% (mean +/- SEM) of the follicles were in anagen VI, whereas none (0%) were in anagen in the control group. Similarly, in induced anagen mice treated with PTH (7-34), 22.3 +/- 1.4 (mean +/- SEM) of the follicles were in anagen VI compared to only 1.3 +/- 0.7% in the control mice. Together these observations suggest that PTHrP is a hair follicle morphogen that may be a major factor responsible for controlling the hair cycle. These studies provide a new insight for development of PTHrP analogs for a wide variety of disorders related to disturbances of hair cycling.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/1523-1747.ep12294690 | DOI Listing |
Arch Oral Biol
June 2022
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Electronic address:
Objective: The aim of this study was to investigate the mechanisms of how protein kinase A (PKA) is activated during bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation in dental follicle stem cells.
Design: Human dental follicle stem cells were cultured and treated with a BMP2-containing osteogenic differentiation medium or differentiation medium without BMP2. Specific siRNAs and substances/proteins were used to modulate pathways.
J Bone Miner Res
May 2021
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Endochondral ossification is tightly controlled by a coordinated network of signaling cascades including parathyroid hormone (PTH). Pleckstrin homology (PH) domain and leucine rich repeat phosphatase 1 (Phlpp1) affects endochondral ossification by suppressing chondrocyte proliferation in the growth plate, longitudinal bone growth, and bone mineralization. As such, Phlpp1 mice have shorter long bones, thicker growth plates, and proportionally larger growth plate proliferative zones.
View Article and Find Full Text PDFACS Chem Biol
October 2016
Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, Massachusetts 02114, United States.
A backbone-modified peptide derived from parathyroid hormone (PTH) is shown to function as an inhibitor and inverse agonist of parathyroid hormone receptor-1 (PTHR1) signaling. This receptor acts to regulate calcium and phosphate homeostasis, as well as bone turnover and development. PTH is a natural agonist of PTHR1, and PTH(1-34) displays full activity relative to the natural 84-residue hormone.
View Article and Find Full Text PDFMatrix Biol
December 2017
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Mechanical loading and release of endogenous parathyroid hormone (PTH) during exercise facilitate the adaptation of bone. However, it remains unclear how exercise and PTH influence the composition of bone and how exercise and PTH-mediated compositional changes influence the mechanical properties of bone. Thus, the primary purpose of this study was to establish compositional changes within osteocytes' perilacunar region of cortical bone following exercise, and evaluate the influence of endogenous PTH signaling on this perilacunar adaptation.
View Article and Find Full Text PDFMol Pharmacol
April 2015
National Institutes of Health, National Institute on Aging, Baltimore, Maryland (S.M., B.M., S.P., K.G.B., W.H.W., Y.Z., E.L.); Department of Medicine, Duke University Medical Center, Durham, North Carolina (D.G.-P.); National Institutes of Health, Center for Information Technology, Bethesda, Maryland (H.C., C.J.); Department of Medicine and Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina (L.M.L.); and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina (L.M.L.).
Biased G protein-coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in cellula efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [d-Trp(12), Tyr(34)]bovine PTH(7-34) in six different murine tissues after chronic drug exposure.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!