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口腔病理科

On-Line KMU Student Bulletin

原文題目(出處): Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation. Head Face Med 2014, 10:8 原文作者姓名: Feller L, Masilana A, Khammissa RAG, Altini M, Jadwat Y,

Lemmer J

通訊作者學校: Department of Periodontology and Oral Medicine, University of Limpopo (Medunsa Campus), Pretoria, South Africa

報告者姓名(組別): 蔡昀蓁 Intern L組

報告日期: 103.7.11

內文:

1. Under physiological conditions the number of melanocytes in the oral epithelium is the same regardless of racial/ethnic origin

一般來說, oral epithelium 的 melanocyte 數目在不同人種間差別不大 2. Oral mucosa 的顏色通常由以下因素決定:

a. Basal cell layer 中 melanocyte 的數目和 melangenic activity b. Melanosome 的數目,大小,分佈

c. Melanins 種類(eumelanin: black-brown/pheomelanin:yellow-red) d.角質化上皮的遮蔽效果

3. Oral mucosa pigmentation 易發生於膚色較深的人(98% of black persons has it),有 patchy 或 uniform 兩種類型,最常影響 gingiva

4. Melanocyte 在 membrane-bound 或 ganelles termed melanosome 中製造出 melanin,melanosome 所含的蛋白質與酵素足以供給 melanin biosynthesis,維持 melanosome 的結構,並讓 immature pre-melanosome 成熟

melanosome 成 熟 後 , 會 經 由 microtibuli 運 送 到 elongated dendrites of the melanocytes 的表面,最後再被傳送到 keratinocyte melanin unit 中的 keratinocyte 中,然後在 nuclei 內形成 supranuclear caps 來防護 UV 的傷

5. Non-physiological alterations in melanin pigmentation of the oral mucosa 與以下 因素相關:

基因,新陳代謝,內分泌,化學/物理因子,感染原,發炎,neoplastic (genetic, metabolic, endocrine, chemical or physical factors, to infective agents and to inflammatory or neoplastic processe)

30%的 case 中 melanoma 發生在 hyperpigmentation 的部位

6. Melanocytes 發源於 neural crest,發育過程中 melanocytes stem cell 會遷移到 skin 和 mucous membranes

Active melanocytes 分布:

stria vascularis of the cochlea/leptomeninges/substantia nigra and locus coerulus of the brain/heart

Melanocyte stem cells 分布:bulge region of hair follicles (epidermal,口腔中未知) 7. Epidermal melanocyte stem cells -> transient- amplifying melanocyte precursors ->

mature melanin producing melanocytes

a. (胎兒)epidermal melanocyte development during embryogenesisz:

Stem cell factor (SCF) and its tyrosine kinase receptor C-kit signalling pathways b. (成人)maintenance of adult melanocyte stem cells, and thus for melanocyte homeostasis : notch signalling pathways

c. Differentiation of melanocyte precursors : ndothelin 1

d. Melanogenesis : micropthalmia-associated transcription factor (MITF) with its cAMP response element

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口腔病理科

On-Line KMU Student Bulletin

8. Precursor melanocyte migrates from skin to basal cell layer 受 c-kit/SCF, endothelin 1&3, HGF, bFGF 調控

跨過 basement membrane 後會釋放出 E-cadherin 幫助與 basal cell layer 中相鄰 keratinocytes 的 intercellular communication

這些 precursor 如果滯留在 lamina propria/dermis 的話就會形成痣 9. fibroblasts 會影響 melanocyte 的 functional activity

10.keratinocytes 能 夠 控 制 dendritic melanosome transfer 是 因 為 capacity of keratinocytes to phagocytose the melanosomes 由 keratinocytes 表面 protease- activated receptor 2 (PAR-2)控制

11. a. Melanocyte 可調控 keratinocyte 的 functional activity

b. keratinicyte 可藉由 paracrine 的方式調控 melanocyte melanogenesis,而這 些介質包括α-MSH, ACTH, β- endorphin, bFGF, endothelins, HGF 和 SCF 然而我 們對於這些調控機制的瞭解仍是粗略

12. Melanocyte 的功能包括決定眼睛頭髮的顏色,降低環境中 UV radiation, reactive oxygen species (ROS) 和 free radicals 的傷害,sequester metal ions ,bind certain drugs and organic molecules

13. Intermediates of melanogenesis

a. Toxic or mutagenic: Quinones and semiquinones

b. Down regulating immune and inflammatory responses: L-dopa(inhibit the

production of proinflammatory cytokines by T lymphocytes and monocytes)

c. Neutralize ROS generated: Melanins produced by melanocytes residing in the basal cell layer of the gingival epithelium

(dentogingival plaque-in- duced inflammation in the periodontal microenvironment) 14. Melanin 可以 inhibit proliferation of bacterial and fungal microorganisms

an integral part of the innate immune system with a role in neutralising the products of superficial bacterial and fungal infective agents melanogenesin

a. Melanocortin system through the cAMP/MITF pathway can stimulate proliferation of undifferentiated melanocytes

b. α-MSH can stimulates melanogenesis, and also downregulates inflam- matory responses

c. Epidermal adrenergic signalling pathway increase melanin biosynthesis and the number and complexity of melanocytic dendrites

d. Adrenalin/ β2-adrenoceptor/cAMP/MITF pathway

e. Mediators of inflammation such as histamine and ara- chidonic acid metabolites trigger melanogenesis

17. 病理性的 oral pigmentations:

Addison’s disease, neurofibromatosis, oral melanotic maculae, oral mucosal melanoma, drug-induced oral mucosal pigmentation, Kaposi sarcoma, vascular malformations, haemangioma

18. Physiological melanin pigmentation

男女比例差不多,無症狀的,solitary or multiple brown maculae with well-defined borders

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口腔病理科

On-Line KMU Student Bulletin

a. 最常發生在 gingiva,多為 bilaterally symmetrical 並且不會超過 mucogingival junction,有些時候亦不會影響 free gingiva

b.會在二十歲之前逐漸顯現,並且隨著年齡增長而擴大,加深顏色 c. More extensive in the anterior than in the posterior portion of the mouth

d. Buccal/labial surfaces are more intensely pigmented than the lingual/palatal surfaces

題號 題目

1 Which following disease do not cause melanin pigmentation ? (A) Peutz-Jeghers syndrome

(B) Addison disease

(C) Chronic pulmonary disease (D) Ranula

答案(D) 出處:oral and maxillofacial pathology 3edition P.316~318, 456~457 題號 題目

2 Which of the following is the ideal way to distinguish physiological melanin pigmentation from smoker’s melanosis ?

(A) Medical history

(B) Common in anterior gingiva (C) Diffuse pigmentation

(D) Increased melanin pigmentation in basal cell layer 答案(A) 出處: oral and maxillofacial pathology 3edition P.106~114

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