Houpis Constantinos H, Tosios Konstantinos I, Papavasileiou Dimitrios, Christopoulos Panagiotis G, Koutlas Ioannis G, Sklavounou Alexandra, Alexandridis Constantinos
Department of Oral Pathology and Surgery, Dental School, National and Kapodestrian University of Athens, Athens, Greece.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Mar;109(3):415-24. doi: 10.1016/j.tripleo.2009.09.026. Epub 2010 Jan 8.
Parathyroid hormone-related peptide (PTHrP) binds to the parathyroid hormone receptor type 1 (PTHR1), which results in the activation of pathways in osteoblasts that promote osteoclastogenesis through the RANK/RANKL system. RANK/RANKL expression has been shown in central giant cell granuloma of the jaws but PTHrP/PTHR1 has not. MSX1 protein is a classical transcription regulator which promotes cell proliferation and inhibits cell differentiation by inhibiting master genes in tissues such as bone and muscle. It has been implicated in the pathogenesis of cherubism, and its expression has been reported in a single central giant cell granuloma (CGCG) case. We aimed, therefore, to study the expression of those proteins by the different cellular populations of central and peripheral giant cell granulomas (PGCGs) of the jaws.
Twenty cases of CGCG and 20 cases of PGCG of the jaws were retrospectively examined by immunohistochemistry for the percentage of positively staining cells to antibodies for PTHrP, PTHR1, and MSX1, using a semiquantitative method.
In both CGCG and PGCG of the jaws, PTHrP and PTHR1 were abundantly expressed by type I multinucleated giant cells (MGC) and mononucleated stromal cells (MSC) with vesicular nuclei, whereas type II MGC and MSC with pyknotic nuclei expressed those proteins to a lesser extent. In both CGCG and PGCG of the jaws, MSX1 was abundantly expressed by type I MGC and MSC but type II MGC did not express it. A statistically significant difference (P < .05) was observed between CGCG and PGCG in the expression of PTHrP in type II MGC and MSC with pyknotic nuclei and in the expression of PTHR1 in type II MGC.
We suggest that in CGCG and PGCG of the jaws, PTHrP-positive immature osteoblasts activate PTHR1-positive mature osteoblasts to produce RANKL which interacts with RANK on the PTHrP/PTHR1-positive osteoclast-precursor cells found in abundance in the stroma of giant cell lesions and induces osteoclastogenesis through the classic pathway. Cells of the jawbones, the periodontal ligament, or the dental follicle, originating from the neural crest, may be involved in the pathogenesis of giant cell lesions of the jaws. Further study is required for these suggestions to be proved.
甲状旁腺激素相关肽（PTHrP）与1型甲状旁腺激素受体（PTHR1）结合，这会导致成骨细胞中的信号通路被激活，这些信号通路通过RANK/RANKL系统促进破骨细胞生成。RANK/RANKL的表达已在颌骨中央巨细胞肉芽肿中得到证实，但PTHrP/PTHR1的表达尚未得到证实。MSX1蛋白是一种经典的转录调节因子，它通过抑制骨骼和肌肉等组织中的主控基因来促进细胞增殖并抑制细胞分化。它与 cherubism的发病机制有关，并且在一例中央巨细胞肉芽肿（CGCG）病例中报道了其表达情况。因此，我们旨在研究颌骨中央和外周巨细胞肉芽肿（PGCG）不同细胞群体中这些蛋白的表达情况。
采用半定量方法，通过免疫组织化学回顾性检测20例颌骨CGCG和20例颌骨PGCG中PTHrP、PTHR1和MSX1抗体阳性染色细胞的百分比。
在颌骨CGCG和PGCG中，I型多核巨细胞（MGC）和具有泡状核的单核基质细胞（MSC）大量表达PTHrP和PTHR1，而具有固缩核的II型MGC和MSC表达这些蛋白的程度较低。在颌骨CGCG和PGCG中，I型MGC和MSC大量表达MSX1，但II型MGC不表达。在具有固缩核的II型MGC和MSC中PTHrP的表达以及在II型MGC中PTHR1的表达方面，CGCG和PGCG之间观察到统计学上的显著差异（P < 0.05）。
我们认为，在颌骨CGCG和PGCG中，PTHrP阳性的未成熟成骨细胞激活PTHR1阳性的成熟成骨细胞以产生RANKL，RANKL与巨细胞病变基质中大量存在的PTHrP/PTHR1阳性破骨细胞前体细胞上的RANK相互作用，并通过经典途径诱导破骨细胞生成。源自神经嵴的颌骨、牙周韧带或牙囊细胞可能参与颌骨巨细胞病变的发病机制。这些推测有待进一步研究证实。
