Hypophosphatasia may lead to bone fragility: don't miss it.

Hypophosphatasia is an inheritable disorder characterised by defective bone mineralisation due to the impaired activity of tissue-non-specific alkaline phosphatase (AP). Clinical presentation ranges from stillbirth without mineralised bone to pathological fractures in late adulthood. During childhood, the main manifestations include rickets, growth delay and dental problems. Fractures and bone pain usually characterise the adult form. A 9-year-old girl was referred for repetitive fractures after minimal trauma. She had normal growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister had also presented fractures. The proband, her sister and mother had low total and bone-specific AP levels and E435K mutation in exon 12 of the liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone fragility and repetitive fractures may be symptoms of hypophosphatasia in childhood, which must not be neglected. Associated factors such as vitamin D or calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be forgotten as an aetiological factor of repetitive fractures or bone pain in children and AP activity should be checked accurately.

Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro.

The dental follicle (DF) surrounding the developing tooth germ is an ectomesenchymal tissue composed of various cell populations derived from the cranial neural crest. Human dental follicle cells (HDFC) are believed to contain precursor cells for cementoblasts, periodontal ligament cells, and osteoblasts. Bone morphogenetic proteins (BMPs) produced by Hertwig's epithelial root sheath or present in enamel matrix derivatives (EMD) seem to be involved in the control of DF cell differentiation, but their precise function remains largely unknown. We report the immunolocalization of STRO-1 (a marker of multipotential mesenchymal progenitor cells) and BMP receptors (BMPR) in DF in vivo. In culture, HDFC co-express STRO-1/BMPR and exhibit multilineage properties. Incubation with rhBMP-2 and rhBMP-7 or EMD for 24 h increases the expression of BMP-2 and BMP-7 by HDFC. Long-term stimulation of these cells by rhBMP-2 and/or rhBMP-7 or EMD significantly increases alkaline phosphatase activity (AP) and mineralization. Expression of cementum attachment protein (CAP) and cementum protein-23 (CP-23), two putative cementoblast markers, has been detected in EMD-stimulated whole DF and in cultured HDFC stimulated with EMD or BMP-2 and BMP-7. RhNoggin, a BMP antagonist, abolishes AP activity, mineralization, and CAP/CP-23 expression in HDFC cultures and the expression of BMP-2 and BMP-7 induced by EMD. Phosphorylation of Smad-1 and MAPK is stimulated by EMD or rhBMP-2. However, rhNoggin blocks only Smad-1 phosphorylation under these conditions. Thus, EMD may activate HDFC toward the cementoblastic phenotype, an effect mainly (but not exclusively) involving both exogenous and endogenous BMP-dependent pathways.