東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

PTH Signaling in Ctsk+ Cells Is Crit...

Seth, Ridhima,

Linked to FindBook

Google Book

Amazon

博客來

PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption /

Record Type:	Electronic resources : Monograph/item
Title/Author:	PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption // Ridhima Seth.
Author:	Seth, Ridhima,
Description:	1 electronic resource (39 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-10, Section: B.
Contained By:	Dissertations Abstracts International86-10B.
Subject:	Dentistry. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31293946
ISBN:	9798310397569

PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption /
Seth, Ridhima,

PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption /Ridhima Seth. - 1 electronic resource (39 pages)

Source: Dissertations Abstracts International, Volume: 86-10, Section: B.

PTH signaling is of primordial clinical importance in the regulation of skeletal development and homeostasis, as well as in tooth formation and eruption. Both skeletal and dental mesenchymal cells express PTH1r and are target of PTH signaling. Our lab has been investigating the function of a recently identified periosteal stem cell (PSC) population labeled by Cathepsin K (Ctsk) in the regulation of cortical bone homeostasis. Ctsk+ lineage PSCs, which fulfil stemness criteria, express high levels of the PTH1r and respond to iPTH treatment. Ctsk is also expressed in dental pulp cells, dental follicle cells, and the periodontal ligament which are known to play a key role in tooth development and eruption. Whether PTH signaling in Ctsk+ lineage cells is required for proper periosteal bone formation and tooth development and eruption is not known. We, therefore, undertook a study to investigate whether PTH signaling in the Ctsk expressing PSCs and dental mesenchymal cells regulates these processes. To this end, we generated mice lacking PTH1r, specifically in Ctsk+ cells, using the CtskCre mice and analysed their cortical bone and teeth.Eight-week-old CtskCre;PTH1rfl/fl (CtskPTH1r) male and female mice are significantly smaller than their control littermates (PTH1rfl/fl). microCT and bone histomorphometry analyses revealed a significant decrease in cortical bone volume (%), cortical thickness, and periosteal MAR in CtskPTH1r mice compared to PTH1rfl/fl littermates. Notably, CtskPTH1r male and female mice present with failure of molar eruption and impaired incisor eruption. microCT analyses and histological examination revealed several abnormalities in 8-week-old CtskPTH1r mice, including truncated molar roots, loss of the periodontal ligament, root ankylosis, reduced cementoblasts, and markedly decreased alveolar bone. Severe dental anomalies werealso seen in CtskPTH1rmice at P12 and P19. Confirming that both the skeletal and the tooth phenotype are a consequence of deletion of the PTH1r in the mesenchymal cell lineage, Lys2Cre mice, widely used to deleted genes of interest in osteoclasts, do not present with any skeletal and dental phenotype.While our findings confirm the significance of PTH signaling in both periosteal bone formation and tooth development and eruption, they reveal for the first time a crucial role for Ctsk+ lineage cell- dependent PTH signaling within the periosteum and dental mesenchyme. The periosteum is a significant source of stem cells and progenitors contributing to bone growth and homeostasis, regeneration and response to anabolic drugs. Investigating the signaling molecules and pathways regulating periosteal stem cells offers an opportunity to advance our understanding of the mechanisms involved in these processes and may open novel and targeted therapeutic approaches for human diseases associated with bone fragility and impaired bone regeneration. Similarly, a comprehensive understanding of distinct subsets of dental mesenchymal cell populations and unravelling their regulation is of significance for the effective pursuit of novel dental regenerative strategies.

English

ISBN: 9798310397569Subjects--Topical Terms:

828971
Dentistry.
Subjects--Index Terms:

Cathepsin K

PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption /
LDR:04691nmm a22004453i 4500 001 2438215
005 20251210113946.5
006 m o d
007 cr|nu||||||||
008 261011s2024 miu||||||m |||||||eng d
020 $a 9798310397569
035 $a (MiAaPQD)AAI31293946
035 $a AAI31293946
040 $a MiAaPQD $b eng $c MiAaPQD $e rda
100 1 $a Seth, Ridhima, $e author. $0 (orcid)0000-0003-4596-3233 $3 3829453
245 1 0 $a PTH Signaling in Ctsk+ Cells Is Critical for Skeletal Homeostasis and Tooth Formation and Eruption / $c Ridhima Seth.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2024
300 $a 1 electronic resource (39 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 86-10, Section: B.
500 $a Advisors: Gori, Francesca Committee members: Baron, Roland; Rosen, Vicki; Kantarci, Alpdogan; Gamer, Laura.
502 $b D.M.Sc. $c Harvard University School of Dental Medicine $d 2024.
520 $a PTH signaling is of primordial clinical importance in the regulation of skeletal development and homeostasis, as well as in tooth formation and eruption. Both skeletal and dental mesenchymal cells express PTH1r and are target of PTH signaling. Our lab has been investigating the function of a recently identified periosteal stem cell (PSC) population labeled by Cathepsin K (Ctsk) in the regulation of cortical bone homeostasis. Ctsk+ lineage PSCs, which fulfil stemness criteria, express high levels of the PTH1r and respond to iPTH treatment. Ctsk is also expressed in dental pulp cells, dental follicle cells, and the periodontal ligament which are known to play a key role in tooth development and eruption. Whether PTH signaling in Ctsk+ lineage cells is required for proper periosteal bone formation and tooth development and eruption is not known. We, therefore, undertook a study to investigate whether PTH signaling in the Ctsk expressing PSCs and dental mesenchymal cells regulates these processes. To this end, we generated mice lacking PTH1r, specifically in Ctsk+ cells, using the CtskCre mice and analysed their cortical bone and teeth.Eight-week-old CtskCre;PTH1rfl/fl (CtskPTH1r) male and female mice are significantly smaller than their control littermates (PTH1rfl/fl). microCT and bone histomorphometry analyses revealed a significant decrease in cortical bone volume (%), cortical thickness, and periosteal MAR in CtskPTH1r mice compared to PTH1rfl/fl littermates. Notably, CtskPTH1r male and female mice present with failure of molar eruption and impaired incisor eruption. microCT analyses and histological examination revealed several abnormalities in 8-week-old CtskPTH1r mice, including truncated molar roots, loss of the periodontal ligament, root ankylosis, reduced cementoblasts, and markedly decreased alveolar bone. Severe dental anomalies werealso seen in CtskPTH1rmice at P12 and P19. Confirming that both the skeletal and the tooth phenotype are a consequence of deletion of the PTH1r in the mesenchymal cell lineage, Lys2Cre mice, widely used to deleted genes of interest in osteoclasts, do not present with any skeletal and dental phenotype.While our findings confirm the significance of PTH signaling in both periosteal bone formation and tooth development and eruption, they reveal for the first time a crucial role for Ctsk+ lineage cell- dependent PTH signaling within the periosteum and dental mesenchyme. The periosteum is a significant source of stem cells and progenitors contributing to bone growth and homeostasis, regeneration and response to anabolic drugs. Investigating the signaling molecules and pathways regulating periosteal stem cells offers an opportunity to advance our understanding of the mechanisms involved in these processes and may open novel and targeted therapeutic approaches for human diseases associated with bone fragility and impaired bone regeneration. Similarly, a comprehensive understanding of distinct subsets of dental mesenchymal cell populations and unravelling their regulation is of significance for the effective pursuit of novel dental regenerative strategies.
546 $a English
590 $a School code: 2122
650 4 $a Dentistry. $3 828971
650 4 $a Biology. $3 522710
650 4 $a Cellular biology. $3 3172791
653 $a Cathepsin K
653 $a Dental stem cells
653 $a PTH receptors
653 $a Skeletal homeostasis
653 $a Skeletal stem cells
653 $a Tooth development and eruption
690 $a 0567
690 $a 0306
690 $a 0379
710 2 $a Harvard University School of Dental Medicine. $b Oral Biology. $e degree granting institution. $3 3829454
720 1 $a Gori, Francesca $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-10B.
790 $a 2122
791 $a D.M.Sc.
792 $a 2024
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31293946