BackgroundOsteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2−/−) mice.Materials and methodsThe trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.ResultsPLCγ2−/− mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLCγ2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLCγ2−/− mice was similar to, or even more robust than, that in wild-type animals.ConclusionsOur results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency–induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.

The main driver of osteoporosis is an imbalance between bone resorption and formation. The pathogenesis of osteoporosis has also been connected to genetic alterations in key osteogenic factors and dysfunction of bone marrow mesenchymal stem/stromal cells (BM-MSCs). Tks4 (encoded by the Sh3pxd2b gene) is a scaffold protein involved in podosome organization. Homozygous mutational inactivation of Sh3pxd2b causes Frank-ter Haar syndrome (FTHS), a genetic disease that affects bone tissue as well as eye, ear, and heart functions. To date, the role of Tks4 in adult bone homeostasis has not been investigated. Therefore, the aim of this study was to analyze the facial and femoral bone phenotypes of Sh3pxd2b knock-out (KO) mice using micro-CT methods. In addition to the analysis of the Sh3pxd2b -KO mice, the bone microstructure of an FTHS patient was also examined. Macro-examination of skulls from Tks4-deficient mice revealed craniofacial malformations that were very similar to symptoms of the FTHS patient. The femurs of the Sh3pxd2b -KO mice had alterations in the trabecular system and showed signs of osteoporosis, and, similarly, the FTHS patient also showed increased trabecular separation/porosity. The expression levels of the Runx2 and osteocalcin bone formation markers were reduced in the bone and bone marrow of the Sh3pxd2b -KO femurs, respectively. Our recent study demonstrated that Sh3pxd2b -KO BM-MSCs have a reduced ability to differentiate into osteoblast lineage cells; therefore, we concluded that the Tks4 scaffold protein is important for osteoblast formation, and that it likely plays a role in bone cell homeostasis.

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Hazánk európai szinten első helyen áll a szájüregi daganatok számát tekintve, melyek felismerése legtöbbször meglehetősen későn történik, így sokszor rezektív műtétekre kerül sor. Az ezek eredményeként létrejött állapot helyreállítása komoly feladat, ami csapatmunkát igényel. Ebben a teamben fontos szerepe van a fogorvosnak is. A helyreállító protetika a fogpótlástan egy kevéssé előtérben lévő és a hétköznapokban kevésbé tárgyalt ága, holott a páciensek száma hazánkban a fenti okok miatt európai viszonylatban magasnak mondható, ellátásuk pedig sok tervezést, találékonyságot, egyéni megoldást követel. Ebben a közleményben egy mandibula segment resektión átesett páciens rehabilitációján keresztül szeretnénk bemutatni az ellátás nehézségeit. Ilyen esetekben a műtét során eltávolított mandibula segment hiányából ered az összes kompenzálandó probléma, így ugyanis a rágóizmok tapadása megszűnik, ezáltal húzóerejük hatására malocclusio, nyitáskor pedig egy erős deflexió alakul ki. Ezek kompenzálása dupla fogsoros vagy vezetőfelszínnel rendelkező lemezes fogpótlással lehetséges. Az ellátáshoz ez utóbbit választottuk. A hosszas előkészítést követően, a kivitelezés alatti kisebb problémákat leküzdve, egy orvosi szempontból is megfelelő és a páciens számára is komfortos restaurációt tudtunk készíteni.

Background This study aimed to investigate the effect of ovariectomy and vitamin D3 on bone microstructure; this effect was examined in three regions of interest at one femoral and two mandibular sampling sites bone in an ovariectomized mouse model. Methods Thirty-six week-old female mice were randomly divided into three groups: 10 subjects were given oral cholecalciferol (vitamin D3) daily for 6 weeks after undergoing bilateral ovariectomy (D3 group), while 10 ovariectomized subjects (OVX) and 10 subjects who underwent a sham operation (SHAM) received peanut oil daily during the investigation. After extermination, the left hemimandible and femur were removed and scanned by micro-CT. The bone micromorphology parameters were analyzed and the BMD was calculated. Results The bone volume fraction (BV/TV) was significantly lower in the trabecular bone of the mandibular condyle in the OVX group than in the SHAM and D3 groups. Also there was a significant difference between the SHAM and D3 groups. The specific bone surface (BS/BV) was significantly higher in the OVX and D3 groups than in the SHAM group. Trabecular thickness (Tb.Th) was significantly higher in the SHAM group, and the trabecular bone pattern factor (Tb.Pf) was significantly higher in the OVX group than in the other two groups. Bone mineral density (BMD) of the femur and the mandible was significantly lower in the OVX group than in the SHAM and D3 groups. Conclusions Our results show that ovariectomy causes a significantly weaker bone microstructure in the mandibular condyle, where the protective effect of vitamin D3 resulted in a partial resorption.