Elevated Levels of a Disintegrin and Metalloproteinase 8 in Gingival Crevicular Fluid of Patients With Periodontal Diseases

Background: A disintegrin and metalloproteinase 8 (ADAM8) is involved in inflammation and is essential for osteoclastogenesis. Elevated ADAM8 levels are detected in human serum and other body fluids in several inflammatory conditions. Therefore, we hypothesized that ADAM8 levels are also raised in gingival crevicular fluid (GCF) of patients with periodontal diseases. Methods: Forty‐five patients with periodontal diseases (n = 15 for each group: the group of patients with gingivitis, the group with aggressive periodontitis [AgP], and the group with chronic periodontitis [CP]) and 15 volunteers who exhibited healthy gingiva were recruited. Four periodontal parameters, gingival index, plaque index, probing depth, and clinical attachment level, were recorded before GCF collection. The presence of ADAM8 in GCF was shown by immunoblotting using anti‐human ADAM8 polyclonal antibody against its prodomain, and the ADAM8 levels were measured by an enzyme‐linked immunosorbent assay. Results: Four immunoreactive bands at 120, 70, 50, and <30 kDa were detected in the groups of patients with periodontitis, whose intensities were stronger than those in the group of patients with gingivitis, consistent with significantly greater ADAM8 levels in both groups of patients, with either CP or AgP, than those in the group of patients with gingivitis and in the group that was healthy (P <0.001). Moreover, the ADAM8 levels correlated significantly with the four periodontal parameters (P <0.001), indicating that ADAM8 levels are positively associated with the degree of periodontal tissue inflammation and destruction. Conclusions: The ADAM8 levels are elevated in the GCF of patients with periodontal diseases, including gingivitis, CP, and AgP, in comparison to control participants who are healthy, and they correlate with four clinical parameters that reflect the degree of disease severity.     

Traditional chewing and smoking habits from the point of view of Northern Thai betel quid vendors

PURPOSE: To evaluate knowledge of betel quid (BQ) vendors in relation to traditional chewing and smoking habits in Northern Thailand. MATERIALS AND METHODS: Interviews of vendors selling BQ and other traditional chewing and smoking items were conducted. Questions related to side effects of BQC were included, as well as questions focusing on why traditional chewing and smoking habits were on the decline. RESULTS: Nineteen stalls in 10 markets were visited and 18 vendors were interviewed (16 women, 2 men, average age 55.0 years, range 28-75 years). Vendors had been present for an average of 21.8 years (range 2-60 years). The number of customers buying BQ regularly was 2-3 per day. More elderly women than men bought BQ. Side effects of BQ on the oral mucosa were largely unknown to vendors. Most respondants thought BQ to be good for teeth. Reasons why young people have given up the BQ habit were black teeth. Miang (fermented tea leaves) and khi yo (traditional cigar) were rarely sold and were considered vanishing habits. CONCLUSIONS: BQ vendors had poor knowledge of the side effects of BQC. BQ vendors unanimously considered traditional habits such as chewing of BQ, miang and smoking of traditional cigars to be on the decline. Nowadays, most of these items are bought to be offered during ceremonies. Generally, traditional habits seem to be replaced by 'modern' lifestyle habits such as cigarette smoking and alcohol consumption. With these changes, general and oral disease patterns will eventually occur.     

Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7

Infantile malignant autosomal recessive osteopetrosis (ARO; OMIM 259700) has been reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1. ARO caused by homozygous (or compound heterozygous) mutations in CLCN7, as described here, is usually diagnosed at birth or early in infancy due to generalized osteosclerosis and severe hematologic deficits. The maximal life expectancy of patients with ARO in the absence of bone marrow transplantation is thought to be 10 years. We report on a 25-year-old Thai man who is affected with ARO. Clinical features include proportionate short stature, vision impairment, esotropia, exophthalmos, mild hearing loss, and hepatosplenomegaly. Pancytopenia was present and the patient had frequent illnesses. Radiographs showed generalized osteosclerosis with almost no visible of bone marrow spaces. Dense maxilla and mandible with impacted and malformed teeth were observed. Multiple fractures were reported. He developed osteomyelitis of the mandible on four separate occasions, and partial mandibulectomy was performed. Molecular studies showed that there were no pathogenic mutations in TCIRG1. However, mutation analysis of CLCN7 revealed a homozygous missense mutation (p.Arg526Gln). This patient is, it appears, the longest lived individual with ARO ever reported. Evaluation of osteoclastogenesis in our patient demonstrated very large immature osteoclasts with a high number of nuclei.     

CLCN7 and TCIRG1 Mutations Differentially Affect Bone Matrix Mineralization in Osteopetrotic Individuals

Osteopetrosis is an inherited disorder of impaired bone resorption, with the most commonly affected genes being CLCN7 and TCIRG1, encoding the Cl^?/H⁺ exchanger CLC‐7 and the a3 subunit of the vacuolar H⁺‐ATPase, respectively. We and others have previously shown that the disease is frequently accompanied by osteomalacia, and that this additional pathology is also found in Tcirg1‐deficient oc/oc mice. The remaining question was whether osteoid enrichment is specifically associated with TCIRG1 inactivation, or whether CLCN7 mutations would also cause skeletal mineralization defects. Here we describe a complete osteologic assessment of one family carrying a novel mutation in CLCN7 (D145G), which impairs the activation and relaxation kinetics of the CLC‐7 ion transporter. The two siblings carrying the mutation in the homozygous state displayed high bone mass, increased serum levels of bone formation markers, but no impairment of calcium homeostasis when compared to the other family members. Most importantly, however, undecalcified processing of an iliac crest biopsy from one of the affected children clearly demonstrated a pathological increase of trabecular bone mass, but no signs of osteomalacia. Given the potential relevance of these findings we additionally performed undecalcified histology of iliac crest biopsies from seven additional cases with osteopetrosis caused by a mutation in TNFRSF11A (n = 1), CLCN7 (n = 3), or TCIRG1 (n = 3). Here we observed that all cases with TCIRG1‐dependent osteopetrosis displayed severe osteoid accumulation and decreased calcium content within the mineralized matrix. In contrast, there was no detectable bone mineralization defect in the cases with TNFRSF11A‐dependent or CLCN7‐dependent osteopetrosis. Taken together, our analysis demonstrates that CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization, and that there is a need to modify the current classification of osteopetrosis. © 2014 American Society for Bone and Mineral Research.