Application of Developmental Principles for Functional Regeneration of Salivary Glands

Eui-Seon Lee; Nirpesh Adhikari; Jae-Kwang Jung; Chang-Hyeon An; Jae-Young Kim; Ji-Youn Kim

doi:10.11637/aba.2019.32.2.83

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Lee, Adhikari, Jung, An, Kim, and Kim: Application of Developmental Principles for Functional Regeneration of Salivary Glands

Review Article

Anat Biol Anthropol 2019;32(3):83-91.

Published online: 20 January 2019

DOI: https://doi.org/10.11637/aba.2019.32.2.83

Application of Developmental Principles for Functional Regeneration of Salivary Glands

Eui-Seon Lee¹, Nirpesh Adhikari¹, Jae-Kwang Jung², Chang-Hyeon An³, Jae-Young Kim^1,, Ji-Youn Kim^4∗

¹Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University

²Department of Oral Medicine, School of Dentistry, Kyungpook National University

³Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyungpook National University

⁴Department of Dental Hygiene, College of Health Science, Gachon University

Correspondence to: Jae-Young Kim (Department of Oral Biochemistry, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, Republic of Korea) & Ji-Youn Kim (Department of Dental Hygiene, College of Health Science, Gachon University, 191 Hambang-moe-ro, Yeonsu-gu, Incheon, Republic of Korea) E-mail: jykim91@knu.ac.kr & hoho6434@gachon.ac.kr

Received 25 April 2019 Revised 6 June 2019 Accepted 20 August 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Currently, there has been rapid increase in the studies about salivary production because of the hyposalivation, xerostomia, caused by radiotherapy for head and neck cancer, Sjogren syndrome and aging. An overview of anatomy and development of salivary gland is crucial to understand about the patho-physiological disorders related with saliva. For study of the morphogenesis and development of salivary glands, experiment using rodent models is widely necessary. This review wraps up the early to latest studies – the different features of each salivary gland, morphogenesis of developing salivary glands, and the comparison of human and rodent salivary glands. The goal of this review is to provide hypothesis for the further researches about differentiation of specific acinar cells, from which it is determined to be specific acini. Additionally, we discuss approaches to regenerate the function of salivary glands using environmental factor, time dependent factor and nerve factor.

Keywords: Salivary gland development, Morphogenesis of salivary gland, Rodent salivary glands

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Fig. 1.

Anatomy of the anterior neck portions of developing salivary glands of mice (a-c). Embryonic day 16.5 (E16.5), post-natal day 0 (PN0) and adult mice showing the location of parotid gland, submandibular gland and sublingual gland. Scale bars, 1 mm.

Fig. 2.

Hematoxylin and eosin staining of the developing parotid gland (PG; a, c, e) and sublingual gland (SLG; b, d, f). Embryonic day 15.5 PG showing epithelial bud (a). Post-natal day 0 (PN0) PG showing terminal epithelial buds (c). Adult PG showing dark-colored acinar cells which characterizes serous acinar cell (e). E15.5 SLG with developing epithelial end buds and lumen formation (b). PN0 showing terminal tu-bules and differentiating acinar cells (d). Adult SLG showing light-colored acinar cells which characterizes mucous acinar cells (f). TT terminal tubule, ED excretory duct, SC serous acinar cell, ME myoepithelial cell, MC mucous acinar cell.

Table 1.

Functions of saliva

Function	Effect	Active constituents
Protection [13]	Clearance	Water
	Clearance Lubrication	Water Mucins, Glycoproteins
	Thermal / Chemical insulation	Mucins
	Pellicle formation	Proteins, Glycoproteins, Mucins
	Tannin binding	Basic proline-rich proteins, Histatins
Buffering [5]	pH maintenance	Bicarbonate, Phosphate, basic proteins, urea, ammonia
Buffering [5]	Neutralization of acids
Tooth integrity [5]	Enamel maturation, repair	Calcium, Phosphate, Fluoride, Statherin, Acidic proline-rich Proteins
Antimicrobial activity [5,14]	Physical barrier	Mucins
	Immune defense	Secretory immunoglobulin A
	Nonimmune defense	Peroxidase, Lysozyme, Lactoferrin, Histatin, Mucins, Agglutinins, Secretory, Leukocyte protease inhibitor, Defensins, and Cathelicidin-LL 37
Tissue repair [14]	Epithelial Wound healing	Growth factors, Trefoil proteins, Regeneration
Digestion [5]	Bolus formation	Water, Mucins
Digestion [5]	Starch, triglyceride digestion	Amylase, Lipase
Taste [15]	Solution of molecules	Water and lipocalins
Taste [15]	Solution of molecules Maintenance of taste buds	Water and lipocalins Epidermal growth factor and Carbonic anhydrase VI

Table adapted from Ten cate's oral histology, 8^th edition; page 254.

Table 2.

Minor salivary glands and contribution to saliva

Name	Location	Type secretion
Labial	Lips	Mixed [16]
Buccal	Cheeks	Mixed [16]
Palatine	Hard and soft	Pure mucous [16]
Lingual	Anterior	Mixed
	Middle	Serous
	Posterior	Pure mucous [16]

Table 3.

Signaling genesis pathways involved in salivary gland morpho-

End bud formation	FGF family
	EGF family
	BMP family
	EDA / EDAR
	EDA/ EDAR HSPGs (Heparan sulfate proteoglycans) [43]
Cleft formation	HSPGs
	HSPGs Collagens
	Laminins
	Fibronectin
	FGF family
Lumen formation	Wnt signaling
	EDA / EDAR
	HH signaling
	VIP (Vasoactive intestinal peptide) [44]
Duct formation	Wnt signaling
	EDA / EDAR
	EGF family
	HH signaling
	Notch signaling
	VIP

Table 4.

Characteristics of major salivary glands

	Parotid gland	Submandibular gland	Sublingual gland
Developmental origin [5]	Ectodermal	Endodermal	Endodermal
Opening of the ducts	Buccal cavity across the maxillary second molar [24]	Floor of buccal cavity at the sides of lingual frenulum [17,18,24]	Floor of buccal cavity at the sides of lingual frenulum [18]
Type cells	Serous [5]	Mixed (serous and mucous) [5]	Mostly mucous [5]
Types of acini	Serous acini	Sero-mucous acini	Mostly mucous acini
Specific duct	Stensen's duct [1,5]	Wharton's duct [5]	Duct of Rivinus Bartholin's duct [1,5] – connects with Wharton's duct
Duct types	Three types intercalated, striated and excretory ducts	Three types intercalated, striated and excretory ducts and GCT in case of rodents	Three types intercalated, striated and excretory ducts
Nerve supply	Glossopharyngeal nerve (CN IX), Trigeminal nerve (CN V) [25]	Lingual nerve (Branch of CN V) & Facial nerve (CN VII) [26]	Lingual nerve (Branch of CNV) & Facial nerve (CN VII) [26]
Amount of saliva production	25% of total saliva production [16,24]	60% of total saliva production [2,27]	5% of total saliva production [16]
Size of the glands	Largest among all [18]	Intermediate	Smallest among all [18]

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