Parathyroid hormone–related peptide (PTHrP), parathyroid hormone/parathyroid hormone–related peptide receptor 1 (PTHR1), and MSX1 protein are expressed in central and peripheral giant cell granulomas of the jaws

Houpis, Constantinos; Tosios, Konstantinos I.; Papavasileiou, Dimitrios; Christopoulos, Panagiotis; Koutlas, Ioannis G.; Sklavounou, Alexandra; Alexandridis, Constantinos

doi:10.1016/j.tripleo.2009.09.026

Cited by 18 publications

(16 citation statements)

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“…In addition, the transcription factor Msx-1 mediates the innate cellular plasticity of CNC and is expressed exclusively in CNC-derived bone and bone progenitor structures including oral periost and periodontal ligamentum (PDL) throughout adolescence [10,11]. Within the jaw, Msx-1 is expressed with the highest concentration in the PDL [9,11-13] and is co-expressed with RANKL on CNC-derived osteoblast and chondroblast progenitors [14-16]. Because of the restriction of Msx-1 to the adult jaw and its co-expression with RANKL, a BP- and denusomab-related loss of RANKL and Msx-1 expression might explain the BP- and denosumab-related impairment of hard and soft tissue remodeling that is restricted to the jaw bone in ONJ [4,14].…”

Section: Introductionmentioning

confidence: 99%

“…Within the jaw, Msx-1 is expressed with the highest concentration in the PDL [9,11-13] and is co-expressed with RANKL on CNC-derived osteoblast and chondroblast progenitors [14-16]. Because of the restriction of Msx-1 to the adult jaw and its co-expression with RANKL, a BP- and denusomab-related loss of RANKL and Msx-1 expression might explain the BP- and denosumab-related impairment of hard and soft tissue remodeling that is restricted to the jaw bone in ONJ [4,14]. Thus, the aim of this study was to compare Msx-1, BMP-2/4, and RANKL expression at the protein and mRNA levels in samples of BONJ-related oral mucoperiosteal tissue compared to healthy oral periodontal tissue to test the hypothesized impairment of jaw-specific Msx-1-RANKL-associated cell signaling in periodontal progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

et al. 2010

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BackgroundBone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue.MethodsTwenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels.ResultsSemi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control.ConclusionsThese results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

et al. 2010

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“…[21, 22] Brown tumor of hyperparathyroidism can perforate the cervical region of the tooth and mimic GCG; alternatively, GCG may be the initial presentation of primary hyperparathyroidism or secondary hyperparathyroidism (generally due to renal insufficiency). Consideration of this disorder is particularly important in cases showing signs of hypercalcemia (renal calculi and neuromuscular, gastrointestinal, or psychiatric disorders), since patients with hyperparathyroidism have been reported to show increased blood levels of calcium, as well as parathormone and alkaline phosphates [23, 24]. However, the medical history of the patient was noncontributory.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Giant Cell Granuloma in a Child Associated with Ectopic Eruption and Traumatic Habit with Control of Four Years

Volpato

Leite

Anhesini

et al. 2016

Case Reports in Dentistry

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Peripheral giant cell granuloma (PGCG) is a nonneoplastic lesion that may affect any region of the gingiva or alveolar mucosa of edentulous and toothed areas, preferentially in the mandible and rarely occurring in children. This report describes the clinical and histopathological findings of a PGCG diagnosed in the maxilla of a 9-year-old boy associated with a tooth erupting improperly and a traumatic habit. The patient did not present anything noteworthy on extraoral physical examination or medical history, but the habit of picking his teeth and “poking” the gingiva. The oral lesion consisted of an asymptomatic, rounded, pink colored, smooth surface, soft tissue injury with fibrous consistency and approximated size of 1.5 cm located in the attached gingiva between the upper left permanent lateral incisor and the primary canine of the same side. Excisional biopsy was performed through curettage and removal of the periosteum, periodontal ligament, and curettage of the involved teeth with vestibular access. The histopathological analysis led to the diagnosis of PGCG. The prompt diagnosis and treatment of the PGCG resulted in a more conservative surgery and a reduced risk for tooth and bone loss and recurrence of the lesion. After four years of control, patient had no relapse of the lesion and good gingival and osseous health.

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“…Parathyroid hormone--like hormone (PTHLH) contributes to skeletal growth and development [10] in children. The PTH receptors were also included in this analysis because PTH1R binds with PTH/PTHLH promoting osteoclastogenesis [11], while PTH2R has been implicated in endochondral bone formation [12] and is specific for PTH rather than PTHLH. Since degeneration in the lower spine may be linked to both osteoporosis and osteoarthritis resulting from the anatomical structure and loading pattern on the spine, there may be pleiotropic gene--effects associated with the manifestations.…”

Section: Introductionmentioning

confidence: 99%

Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine

et al. 2013

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Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine. Link to publication Citation for published version (APA): Åkesson, K., Tenne, M., Gerdhem, P., Luthman, H., & McGuigan, F. (2015). Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine. Journal of Bone and Mineral Metabolism, 33(1), 9-15. DOI: 10.1007/s00774-013-0550-x General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal

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Parathyroid hormone–related peptide (PTHrP), parathyroid hormone/parathyroid hormone–related peptide receptor 1 (PTHR1), and MSX1 protein are expressed in central and peripheral giant cell granulomas of the jaws

Cited by 18 publications

References 67 publications

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

Peripheral Giant Cell Granuloma in a Child Associated with Ectopic Eruption and Traumatic Habit with Control of Four Years

Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine

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