Type II Collagen Accumulation in Overlying Dermo-Epidermal Junction of Pilomatricoma Is Mediated by Bone Morphogenetic Protein 2 and 4

Abstract

Pilomatricoma consists of the cells differentiating towards hair matrix cells. Immunohistochemical study revealed the deposition of type II collagen in the overlying dermo-epidermal junction (DEJ) of this benign tumor. Proalpha(1)(II) mRNA was detected by RT-PCR in the overlying epidermal layer but not in the dermal layer prepared from the lesional skin of pilomatricoma. The neutral salt-soluble proteins extracted from the tumor of pilomatricoma induced proalpha(1)(II) mRNA in the cultured human keratinocytes but not in the cultured dermal fibroblasts. Bone morphogenetic protein 2 or 4 (BMP2 or 4) was immunohistochemically detected in some shadow cells of pilomatricoma. Recombinant BMP2 and BMP4 were found to induce proalpha(1)(II) mRNA concentration dependently in the cultured human keratinocytes but not in the cultured fibroblasts. Proalpha(1)(II) mRNA induced by BMP2 and in cultured keratinocytes contained exon 2, indicating that the mRNA species is non-chondrogenic type IIA form. The results strongly suggest that BMP2 or 4 expressed in pilomatricoma is responsible for the induction of proalpha(1)(II) collagen mRNA in the overlying epidermal cells resulting in the deposition of type II collagen in the DEJ. When human keratinocytes were cultured on type II collagen substratum in vitro, the cell proliferation was accelerated at the early period of culture but was inhibited at the late period of culture, whereas the cell proliferation was persistently accelerated by type I or IV collagen substratum. Type II collagen deposition in the DEJ may potentially exert profound effects on keratinocyte proliferation and differentiation.

Bone morphogenetic protein‐mediated type II collagen expression in pilomatricoma and cutaneous mixed tumor

“…We have previously reported type II collagen accumulation in the overlying dermo-epidermal junction (DEJ) of pilomatricoma which is mediated by BMPs 2 and 4 produced by SCs of pilomatricoma. 11 In the present study, we extended our studies to a large number of hair follicle-related tumors including pilomatricoma, trichilemmoma, trichoepithelioma, trichofolliculoma, and CMT, and found type II collagen deposition in the overlying DEJ and tumor cell components as well as BMP expression in tumor cells in pilomatricoma and CMT. Because it has been shown that cultured keratinocytes are induced to express type II collagen by BMP in vitro, the BMPtype II collagen interaction may commonly operate in two distinct benign tumors.…”

“…We, for the first time demonstrated that type II collagen was detected in the SCs as well as in the overlying DEJ of pilomatricoma. In our previous article, we focused type II collagen expression in the overlying DEJ of pilomatricoma 11 and were not aware of type II collagen in tumor component of pilomatricoma. Because double immunofluorescence study on the BMP þ /SC þ cases of pilomatricoma revealed that some SCs were double-labeled with both antitype II collagen and anti-BMP antibodies (Fig.…”

“…Our previous experiments using cultured keratinocytes demonstrated that type II collagen-inducing activity of BMP was dose-dependent and became evident at the doses higher than 100 ng/ml. 11 A certain level of local concentration of BMP will be required for type II collagen induction.…”

“…We also found considerable number of BMP-negative (BMP -) cases in pilomatricoma and CMT. The occurrence of the cases with BMP -/DEJ þ or BMP -/ SC þ in pilomatricoma, and BMP -/DEJ þ or BMP -/ CM þ in CMT is relatively rare but hardly negligible (case number 1,8,9,11,14,21, and 34 in pilomatricoma, case number 2 in CMT). The BMP þ cases in pilomatricoma were found to be unrelated to chronological stage of pilomatricoma.…”

“…These tumors were histologically diagnosed with hematoxylin and eosin staining. Four cases of pilomatricomas, which had been reported previously 11 , were included in the present study. Pilomatricomas were histologically classified into four chronological stages; early, fully developed, early regressive (ER), and late regressive (LR) according to the previous report by Kaddu et al 13 Early lesions have small cystic structures lined by squamoid and basaloid epithelium containing keratin filaments and faulty hair-matrix material composed of SCs.…”