Calcium pyrophosphate deposition disease of the temporomandibular joint invading the middle cranial fossa:Two case reports

BACKGROUND Pseudogout is a benign joint lesion caused by the deposition of calcium pyrophosphate dihydrate crystals,but it is invasive.Pseudogout of the temporomandibular joint(TMJ)is uncommon,and it rarely invades the skull base or penetrates into the middle cranial fossa.The disease has no characteristic clinical manifestations and is easily misdiagnosed.CASE SUMMARY We present two cases of tophaceous pseudogout of the TMJ invading the middle cranial fossa.A 46-year-old woman with a history of diabetes for more than 10 years was admitted to the hospital due to swelling and pain in the right temporal region.Another patient,a 52-year-old man with a mass in the left TMJ for 6 years,was admitted to the hospital.Maxillofacial imaging showed a calcified mass and severe bone destruction of the skull base in the TMJ area.Both patients underwent excision of the lesion.The lesion was pathologically diagnosed as tophaceous pseudogout.The symptoms in these patients were relieved after surgery.CONCLUSION Tophaceous pseudogout should be considered when there is a calcified mass in the TMJ with or without bone destruction.A pathological examination is the gold standard for diagnosing this disease.Surgical treatment is currently the recommended treatment,and the prognosis is good after surgery.

Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

Biocalcification crisis in the continental shelf under ocean acidification

Ocean acidification(OA)is a persistent challenge for humans and is predicted to have deleterious effects on marine organisms,especially marine calcifiers such as coral and foraminifera.Benthic foraminifera is an important component of sediment in the continental shelf,while little is known about the impact of ocean acidification on benthic foraminifera both at the community and individual level and associated calcium carbonate deposition.We conducted eight months continued culture experiment under the scenario of 400,800,1200 and 1600 ppm pCO_(2)gradients on living benthic foraminifera from four stations in the continental shelf of the West Pacific Ocean.Statistic results showed OA had a negative effect on the abundance of benthic foraminifera.In contrast,the diversity increased roughly under OA conditions implying OA might stimulate the emergence of rare species and promote community diversity to some extent.In addition,we confirmed that the offshore area wasn’t the refuge for benthic foraminifera while the nearshore one had more resistance to moderate acidification.Calcareous species Protelphidium tuberculatum was the dominant species occupying on average 75%in all treatments and its shell diameter,weight and thickness showed a decrease,indicating the decrease of calcification of benthic foraminifera.A relationship between the weight of P.tuberculatum and pCO_(2)(R^(2)=0.96)was established.Based on the present work,calcareous benthic foraminifera deposited 8.57104 t calcium carbonate per year and this might reduce by nearly half and 90%under 800 and 1200 ppm scenarios,which indicates a biocalcification crisis under ongoing OA.This work shows an analogy for palaeoceanic OA and also provides new insights into the sediment of calcium carbonate in the future.

Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy？

Calcifying tendinopathy is a tendon disorder with calcium deposits in the mid-substance presented with chronic activity-related pain, tenderness, local edema and various degrees of incapacitation. Most of current treatments are neither effective nor evidence-based because its underlying pathogenesis is poorly understood and treatment is usually symptomatic. Understanding the pathogenesis of calcifying tendlinopathy is essential for its effective evidence-based management. One of the key histopathological features of calcifying tendinopathy is the presence of chondrocyte phenotype which surrounds the calcific deposits, suggesting that the formation of calcific deposits was cellmediated.Although the origin of cells participating in the formation of chondrocyte phenotype and ossification is still unknown, many evidences have suggested that erroneous tendon cell differentiation is involved in the process. Recent studies have shown the presence of stem cells with self-renewal and multi-differentiation potential in human,horse, mouse and rat tendon tissues. We hypothesized that the erroneous differentiation of tendon-derived stem cells （TDSCs） to chondrocytes or osteoblasts leads to chondrometaplasia and ossification and hence weaker tendon, failed healing and pain, in calcifying tendinopathy. We present a hypothetical model on the pathogenesis and evidences to support this hypothesis. Understanding the key role of TDSCs in the pathogenesis of calcifying tendinopathy and the mechanisms contributing to their erroneous differentiation would provide new opportunities for the management of calcifying tendinopathy. The re-direction of the differentiation of resident TDSCs to tenogenic or supplementation of MSCsprogrammed for tenogenic differentiation may be enticing targets for the management of calcifying tendinopathy in e future.

Induction of osteoblast differentiation in human adipose derived stem cells by lanthanum ions

Adipose derived stem cells represent a readily available source of adult stem cells for various biomedical applications. In this study, the proliferation and osteogenic differentiation potential of lanthanum nitrate（La3＋） on human adipose derived mesenchymal stem cells（hADSCs） were investigated for the first time and compared with that of dexamethasone（Dex）. Our results provided evidence that La3＋ at 50 μmol/L concentration promoted proliferation of hADSCs upto 2.4 fold when treated for 21 d in DMEM medium. Treatment of hADSCs with La3＋ containing osteogenic induction medium（α-MEM with ascorbic acid and β-glycerophosphate） for 7 d resulted in higher calcium deposition than that in the presence of Dex（0.1 μmol/L） as shown by Alizarin red S and von Kossa staining. Scanning electron micrographs also showed more extracellular matrix mineralization in the presence of La3＋. After 7 d of treatment with La3＋（10 μmol/L） the expression of RunX2, osteopontin（OP） and osteocalcin（OC） increased 3.4, 5.5 and 2.7 fold respectively. Our results provided evidence that in the presence of La3＋ osteogenic differentiation occurred earlier than that in the presence of Dex.

Effect of Amino-,Methyl- and Epoxy-Silane Coupling as a Molecular Bridge for Formatting a Biomimetic Hydroxyapatite Coating on Titanium by Electrochemical Deposition

The objective of this study was to determine the role of functional groups of silane coupling on bioactive titanium （Ti） surface by electrochemical deposition, and calcium phosphate （CAP） coating, as well as bone cell adhesion and proliferation. Methyl group （-CH3）, amino group （-NH2）, and epoxy group （-glyph name--C（O）C） were introduced onto the bioactive Ti surface using self-assembled monolayers （SAMs） with different silane coupling agents as molecular bridges. The effect of the surface functional groups on the growth features of the CaP crystals was analyzed （including chemical compositions, element content, minerals morphology and crystal structure etc.）. CH3-terminated SAMs showed a hydrophobic surface and others were hydrophilic by contact angle measurement; NH2-terminated SAMs showed a positive charge and others were negatively charged using zeta-potential measurement. Scanning electron microscopy results confirmed that flower-like structure coatings consisting of various pinpoint-like crystals were formatted by different functional groups of silane coupling, and the CaP coatings were multicrystalline consisting of hydroxyapatite （HA） and precursors. CaP coating of CH3-terminated SAMs exhibited more excellent crystallization property as compared to coatings of --NH2 and -C（O）C groups. In vitro MC3T3- El cells adhesion and proliferation were performed. The results showed that CaP coatings on silane coupling functionalized surfaces supported cell adhesion and proliferation. Thus, these functional groups of silane coupling on Ti can form homogeneous and oriented nano-CaP coatings and provide a more biocompatible surface for bone regeneration and biomedical applications.