Study of the cell biology and biochemistry of cherubism.

Abstract

Aims-To establish whether the multinucleate cells in lesions of patients with cherubism are also osteoclasts and if this is the case whether they were responsive to calcitonin; to carry out cytogenetic studies on two members of the same family aVected by cherubism in an attempt to identify any major chromosomal defects; and to perform an in-depth modern biochemical study of four children in the same family. Subjects and methods-Four related children with cherubism were studied. Tissue taken from one of the children at elective decompression of an optic nerve was submitted to in vitro bone resorption studies. Cytogenetic studies were done on two of the children and biochemical studies on all four. Results-The multinucleate cells in the cherubic lesions were shown to be osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed the vitronectin receptor, and resorbed bone. Bone resorption by the cultured multinucleate cells was significantly inhibited by calcitonin. High resolution cytogenetic studies failed to detect any chromosomal abnormalities in two children with cherubism. The biochemistry profile of all four children with cherubism showed that serum calcium, parathyroid hormone, parathyroid related hormone, calcitonin, and alkaline phosphatase were within normal levels. Urine analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and calcium in relation to urine creatinine were measured to assess bone resorption in these children, and the values were at the upper end of the normal range in all four. Conclusions-Further studies are required to determine whether calcitonin treatment will control this grossly deforming disease until the time when the physiological changes that occur at puberty rectify the pathology. It is not recommended that biochemical markers of bone resorption are used in isolation to monitor the activity of cherubism in individuals because the results are based on a small number of children and because of reports of marked interindividual variation in the levels of these markers, particularly in children. (J Clin Pathol 1998;51:831-837)

Aggressive behaviour of cherubism in a teenager: 4-years of clinical follow-up associated with radiographic and histological features

“…The hormones act directly in the inhibition of osteoclastogenesis and/or osteoclasts functions. 3 Radiographic appearances of cherubism have been described as unilocular or multilocular, bilateral radiolucent lesions with ragged, poorly defined borders, located in the mandible, 2,4,9,16 similar to our findings. Furthermore, it was verified that the cortical bone at the mandibular base was thin but not disrupted even though there was expansion of the bone, indicating the benign behaviour of cherubism.…”

“…Small vessels may show perivascular collagen cuffing. Osteoid and bone tissue formation were often seen at the periphery of the lesion tissue, results that have also been observed by Katz and Underhill, 15 Hitomi et al, 22 and Mangion et al 11 Southgate and coworkers 3 established that multinucleated cells in the cherubism are osteoclasts since they synthesized tartrateresistant acid phosphatase, expressed vitronectin receptors, promoted bone resorption at culture and the multinucleated giant cells were inhibited by calcitonin in situ. Treatment of cherubism has not been standardized, making it difficult to indicate a treatment protocol.…”

3BP2 Adapter Protein Is Required for Receptor Activator of NFκB Ligand (RANKL)-induced Osteoclast Differentiation of RAW264.7 Cells

“…Finally, genetic evidence linking 3BP2 to the human genetic bone disease cherubism (31,32) indicates that 3BP2 also plays a crucial role during inflammation and bone remodeling. Cherubism is an autosomal dominant disorder characterized by the erosion of maxillar and mandibular bone with the resultant dental and facial deformity caused by excessive osteoclast activity and giant cell granuloma formation (33). The signaling alterations of a mutant form of 3BP2 as observed in a mouse model of cherubism include increased tumor necrosis factor ␣ production by hyperactive macrophages associated with systemic inflammation, aberrant osteoclast activities, and osteoporosis (32).…”

Cherubism: A Case Report

“…Curettage alone or in combination with surgical contouring has been considered the treatment of choice for aggressive lesions [21]. Pharmacological intervention in form of calcitonin has been suggested but clinical evidence in literature to endorse its application in cherubism is still lacking.…”