Uso de microvibración e inhibidores de la catepsina K en tratamientos de regeneración ósea dental / Use of micro-vibration and cathepsin K inhibitors in dental bone regeneration treatments

Introducción: el hueso está en remodelación constante para mantener la estructura del esqueleto, tener un ciclo de resorción por los osteoclastos y formación de hueso nuevo a cargo de los osteoblastos; el hueso también es susceptible a enfermedades sistémicas, traumas, edad y trastornos genéticos que afectarán el remodelado óseo, produciendo una pérdida masiva de masa ósea regulado por hormonas, citocinas, enzimas, etcétera. El objetivo es realizar una revisión sistemática de artículos que muestren cambio o alteración al utilizar tratamientos con microvibraciones y farmacológicos sobre la catepsina K en el hueso alveolar. Material y métodos: para realizar una comparación entre la efectividad del tratamiento a base de microvibraciones y con inhibidores de la catepsina K, se realizó una revisión sistemática en nueve bases de datos (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO y Springer Link). La población de estudio fueron ratas y ratones. Resultados: en este estudio se incluyeron 20 artículos cuya investigación se realizó en estudios clínicos. En los resultados podemos observar cómo todos los tratamientos de alguna forma mejoran el proceso de remodelado óseo. Es difícil comparar cuál de los tratamientos dentro de cada grupo es mejor que otro, debido a que los resultados expresados son cualitativos. Conclusión: acorde a los resultados expresados se opta por realizar un tratamiento con microvibraciones debido a que el uso de inhibidores de la catepsina K aún no se encuentra completamente desarrollado y no se comprenden sus consecuencias debido a su manera sistémica de actuar (AU)

Introduction: the bone is in constant remodeling to maintain the skeletal structure, having a cycle of resorption by osteoclasts and formation of new bone by osteoblasts, the bone is also susceptible to systemic diseases, trauma, age and genetic disorders that affect bone remodeling, producing a massive loss of bone mass regulated by hormones, cytokines, enzymes, etcetera. The objective is to perform a systematic review of articles that show a change or alteration when using micro-vibration and pharmacological treatments on cathepsin K in the alveolar bone. Material and methods: in order to make a comparison between the effectiveness of micro-vibration and cathepsin K inhibitor treatments, a systemic review was carried out in nine databases (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO and Springer Link). The study population was rats and mice. Results: this study included 20 articles whose research was carried out in clinical studies. In the results we can see how all the treatments in some way improve the bone remodeling process, it is difficult to compare which treatment within each group is better than the other, because the results expressed are qualitative. Conclusion: according to the results expressed, it is decided that it is better to perform a treatment with micro vibrations because the use of cathepsin K inhibitors are not yet fully developed and their consequences are not understood due to their systemic way of acting (AU)

Study on material basis of cathepsin K targeted inhibitor in Erzhi Wan / 药学实践与服务

Objective To investigate the active ingredients and components that inhibiting cathepsin K activity in Erzhi Wan, a classic kidney-tonifying formula. Methods Then-butanol, dichloromethane, ethyl acetate and petroleum ether parts and 30 active components in Erzhi Wan were screened by established high throughput fluorescence methods of inhibit the binding activity of CTSK with Z-FR-MCA substrate, the formation of CTSK and chondroitin sulfate A (CSA) complex activity, and the activity of substrate type I collagen degradation by CTSK. Molecular docking and insoluble collagen substrate binding assays were applied to verify the potential CTSK inhibitors. Results The n-butanol and petroleum ether parts of Erzhi Wan inhibited the formation of CTSK and CSA* complex by more than 90%, the petroleum ether part inhibited the binding of CTSK to substrate Z-FR-MCA by more than 90%, the collagen degradation inhibition rate of CTSK in n-butanol part was more than 95% and that in petroleum ether part was 58.6%. Among the 30 active components, 11 showed that the inhibition rate of CTSK and CSA* complex formation was more than 50%, and 5 components with the inhibition rate of Z-FR-MCA binding activity more than 50%. Finally, there were four components including eclalbasaponin Ⅸ, (-)-epicatechin gallate, nuezhenoside and wedelolactone. The inhibition rate of collagen degradation was more than 50%. Eclipta saponin IX inhibited the binding rate between collagen fibers and CTSK, up to 60%, but all of them failed to dock with CTSK active site. Conclusion There are active components that inhibiting cathepsin K in Erzhi Wan, which mainly exists in the n-butanol ingredients, but the active components is not an active-site inhibitor. It might inhibit the binding of CTSK with oligosaccharides by binding to other sites of CTSK, and then reduce the collagen degradation activity of CTSK.

An in vitro study of the effect of Mycobacterium tuberculosis infection on the expression of bone destruction-related factors in osteoclasts / 中国脊柱脊髓杂志

Objectives:To establish a model of Mycobacterium tuberculosis infection of osteoclasts(OC)and explore the mechanism of Mycobacterium tuberculosis infection on OC.Methods:Peripheral blood mononuclear cells(peripheral blood mononuclear cells,PBMCs)were isolated from healthy volunteers.Receptor activator of nuclear factor-KB ligand(RANKL)and macrophage-colony stimulating factor(M-CSF)were used to make PBMCS into OC,and tartrate resistant acid phosphatase(TRAP)staining was performed on the cells.The constructed kanamycin resistant H37Rv pMV261-GFP green fluorescent strain was resuscitated and cultured with 10％oleic albumin dextrose catalase(OADC),7H9 and kanamycin containing Mycobacterium tuberculosis special liquid medium in an incubator at 37℃ until the optical density(OD)value was about 0.5 at 600nm.The OC cells cultured alone were set as the blank control group.And OC cells were also infected with Mycobacterium tuberculosis at different multiplicity of infection(MOI)for 24h,and MTT colorimetric method was used to detect cell survival rate.The MOI with the highest cell survival rate was selected as experimental MOI,and OC cells infected with H37Rv at experimental MOI were set as the experimental group.Fluorescence microscopy and Mycobacterium tuberculosis acid-fast staining were used to observe the transfection of Mycobacterium tuberculosis at the experimental MOI.Quantitative real-time PCR(qRT-PCR)was used to detect the expressions of non-receptor tyrosine kinase C-src,cathepsin K(CK),carbonic anhydrase 2(CA2),Integrin-β3 and matrix metalloproteinase-9(MMP-9).Immunohistochemistry was used to detect the expressions of P-src,CK,CA2,Integrin-β3 and MMP-9 on the cell surface.Western blot(WB)was used to detect the protein expression levels of P-src,CK,CA2,Integrin-β3,and MMP-9.Results:TRAP staining showed that more than 90％of the cells were OC after 15d of culture,which could be used for experiments.The results of MTT colorimetric assay showed that the cell survival rate was the highest when the MOI was 20:1(P＜0.05).This transfection multiplicity can be used as the concentration of experimental group.Fluorescence microscopy showed that when the transfection multiplicity ratio was 20:1,the green fluorescent Mycobacterium tuberculosis entered the OC and was successfully transfected into the OC.The results of acid-fast staining after infection of OC with Mycobacterium tuberculosis showed that when the MOI was 20:1,the acid-fast Mycobacterium tuberculosis stained red entered OC and was also successfully transfected into OC.The results of qRT-PCR,cell immunohistochemistry,and WB showed that the expressions of MMP-9,CK,C-src,CA2,and Integrin-β3 in the experimental group were higher than those in the blank control group(P＜0.05).Conclusions:Mycobacterium tuberculosis can transfect OC;Compared with the blank control group,the levels of five bone destruction factors in the experimental group transfected with OC by Mycobacterium tuberculosis were increased,suggesting that bone destruction of spinal tuberculosis may be related to this,which may provide a new exploration direction for the diagnosis and treatment of bone tuberculosis diseases.

Do matrix metalloproteinase and cathepsin K inhibitors work synergistically to reduce dentin erosion?

Abstract Objectives To evaluate the effects of matrix metalloproteinase (MMP) and cathepsin K (catK) inhibitors on resistance to dentin erosion. Methodology A total of 96 dentin specimens (3×3×2 mm) were prepared and randomly assigned into four groups (n=24): deionized water (DW); 1 µM odanacatib (ODN, catK inhibitor); 1 mM 1,10-phenanthroline (PHEN, MMP inhibitor); and 1 µM odanacatib + 1 mM 1,10-phenanthroline (COM). Each group was further divided into two subgroups for the application of treatment solutions before (PRE) and after erosive challenges (POST). All specimens were subjected to four daily erosive challenges for 5 d. For each erosive challenge, the specimens in subgroup PRE were immersed in the respective solutions before cola drinks, while the specimens in subgroup POST were immersed in the respective solutions after cola drinks (the immersion duration was 5 min in both cases). All specimens were stored in artificial saliva at 37°C between erosive challenges. The erosive dentin loss (EDL) was measured by profilometry. The residual demineralized organic matrix (DOM) of specimens was removed using type VII collagenase and evaluated by profilometry. Both the EDL and thickness of the residual DOM were statistically analyzed by two-way analysis of variance (ANOVA) and Bonferroni's test (α=0.05). The surface topography and transverse sections of the specimens were observed using SEM. MMPs and catK were immunolabeled in the eroded dentin and in situ zymography was performed to evaluate the enzyme activity. Results Significantly lower EDL was found in the groups ODN, PHEN, and COM than in the control group (all p<0.05), while no significant difference in EDL was found among the groups ODN, PHEN, and COM (all p>0.05). The application sequence showed no significant effect on the EDL of the tested groups (p=0.310). A significantly thicker DOM was observed in the group ODN than in the control group regardless of the application sequence (both p<0.05). The treatment with ODN, PHEN, and COM inhibited the gelatinolytic activity by approximately 46.32%, 58.6%, and 74.56%, respectively. Conclusions The inhibition of endogenous dentinal MMPs and catK increases the acid resistance of human dentin but without an apparent synergistic effect. The inhibition of MMPs and catK is equally effective either before or after the acid challenge.

Decreased levels of cathepsin Z mRNA expressed by immune blood cells: diagnostic and prognostic implications in prostate cancer

Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.

Alcohol extract of eucommia ulmoides oliv. Promotes bone healing in rats with periapical periodontitis / 中国组织工程研究

BACKGROUND: Current research on Eucommia ulmoides Oliv. mainly focuses on its use in the treatment of osteoarthritis that Eucommia ulmoides Oliv. can enhance the healing ability of bone tissue. However, research on its bone repair ability in periapical periodontitis has not been reported. OBJECTIVE: To study the effect of alcohol extract of Eucommia ulmoides Oliv. on cathepsin K expression in periapical periodontitis rats. METHODS: Twenty-four Sprague-Dawley rats were divided into normal control group (n=4) and apical periodontitis group (n=20). In the periapical periodontitis group, a periapical periodontitis model was established after exposure of the dental pulp in the first molar of the right mandible. The normal control group did not deal with any treatment. After 4 weeks of feeding, four rats from each group were taken for micro-CT detection. Bone destruction was quantified to confirm whether the rat model of periapical periodontitis was successfully constructed. After 5 weeks of feeding, the remaining 16 rats with periapical periodontitis were equally randomized into alcohol extract group (given alcohol extract of Eucommia ulmoides Oliv. via intragastric administration, 5 mL/kg per day) and normal saline group (given the same dose of normal saline via intragastric administration every day). After 4 weeks of gavage, four mice from each group were selected to perform micro-CT examination. The ability of alcohol extract of Eucommia ulmoides Oliv. to repair periapical bone tissue was analyzed. First molars of the right mandible from the other four rats in each group were extracted to detect the expression of cathepsin K in the alveolar bone using immunohistochemical staining. RESULTS AND CONCLUSION: Micro-CT results showed that the rat model of periapical periodontitis was successfully constructed as there was a significant difference in the bone resorption volume between the normal control and apical periodontitis groups [(0.223±0.009) mm3 vs. (0.945±0.037) mm3, P=0.00]. After 4 weeks of gavage, the micro-CT results showed that the alcohol extract of Eucommia ulmoides Oliv. significantly reduced the bone resorption volume in the rat model of periapical periodontitis (P < 0.05). Immunohistochemistry results showed that the alcohol extract of Eucommia ulmoides Oliv. significantly inhibited the expression of cathepsin K, a marker of bone destruction, in the rat model of periapical periodontitis. Therefore, these findings indicate that the alcohol extract of Eucommia ulmoides Oliv. can inhibit the expression of cathepsin K and promote the healing of bone tissue in the rats with periapical periodontitis.

Estimation of bone mineral density and its correlations with homocysteine, and various other biochemical bone markers in postmenopausal women

Introduction- Omocysteine (HCY) prevents collagen cross-linking and activates osteoclast function within the bones. Bone mineral density (BMD) may be affected by Hyperhomocysteinemia via Cathepsin K. Aim- To find the correlation of BMD with biochemical bone markers. Methods- BMD was investigated by the DXA scan with the help of the Hologic QDR1000 system. As per WHO guidelines, subjects were divided into three different subsets with; normal bone mass, osteopenia, and osteoporosis. Every subject underwent routine biochemical laboratory investigations, HCY, Vitamin B12, and folic acid levels. Results-Among 355 postmenopausal women, 69% (245) had osteoporosis while 11.27% (40) had normal BMD (mean age, 53 ± 8.35 years) and 19.72% (70) had osteopenia (mean age 52.86 ± 7.93 years). The mean age in the osteoporotic group was 56.49 ± 6.65 years. The mean levels of HCY in the three groups were 15.58± 7.92 μmol/L, 16.13± 7.34μmol/L and 17.05± 5.13μmol/L, respectively. Hip BMD showed a strong inverse correlation with age (r=-0.360, p=0.002), while no significant correlations were found between weight and BMI. PTH was consistently seen to be negatively correlated with BMD at Spine (r=-0.0339, p=0.004), Forearm (r=-0.267, p=0.027), and Hip (r=-0.224, p=0.064). Conclusion- Low BMD is an important problem in postmenopausal female patients. Age and duration of menopause are independent risk predictors for the development of osteoporosis. Vitamin D levels do not predict low BMD in postmenopausal females. Weight is protective for osteoporosis especially at spine and forearm BMD. Vitamin B12 and Hcy levels did not correlate with low BMD.

Effects of the cathepsin K inhibitor with mineral trioxide aggregate cements on osteoclastic activity

OBJECTIVES: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. METHODS: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). RESULTS: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of TNF-α and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). CONCLUSION: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.

Pycnodysostosis caused by CTSK mutation:one pedigree study / 中华内分泌代谢杂志

The purpose of this study was to analyze the clinical characteristics of a patient with pycnodysostosis caused by cathepsin K ( CTSK ) gene mutation and his family members in order to improve the understanding of this rare diseases. A pediatric patient with pycnodysostosis was referred to us when he was eight years old. He presented with elevated bone mineral density, short stature, dentition abnormality and multiple fractures of right tibia. Next generation sequencing ( NGS) and Sanger sequencing confirmed that the proband carried carrying compound heterozygous mutations of cathepsin K(CTSK) gene, including a missense mutation c.440C>T in exon 5 (p.Ala147Val) and a deletion mutation c. 778delA in exon 6 ( p. Ser260AlafsX15) which was inherited from his father. His mother and sister did not carry the above variations. Clinically, it is necessary to differentiate pycnodysostosis from osteopetrosis and other osteosclerotic diseases.

Picnodisostosis familiar, reporte de un caso tras 10 años de seguimiento / Family picnodisostosis, report of a case after 10 years of follow-up

Resumen: Introducción: La picnodisostosis es una rara enfermedad secundaria en una mutación en el gen 1q21 que codifica la catepsina K, enzima implicada en el metabolismo de osteonectina, osteopontina y colágeno I. La incidencia mundial es de 1-1.7 casos por millón, sin prevalencia por género, se caracteriza clínicamente por talla baja, deformidades craneales, «cara de pájaro¼ y fragilidad ósea con tendencia a fracturas patológicas, que afectan predominantemente los huesos largos y ocasionalmente en los pedículos vertebrales. Radiológicamente es característica la presencia de osteoesclerosis con canales medulares permeables. Aunque existen numerosos reportes de casos clínicos en la literatura, pocos son los que describen familias con más de un individuo afectado y el seguimiento suele ser a corto plazo. Objetivo: Analizar la evolución clínica de los pacientes afectados. Material y métodos: Se realizó estudio retrospectivo, descriptivo, observacional de tres pacientes con diagnóstico de picnodisostosis, en el período de Julio 2006 a Marzo de 2016. Resultados: Se observaron diferentes formas de afectación de la picnodisostosis, algunas de ellas atípicas como la espondilólisis y una fractura de escápula en una paciente. Conclusiones: El presente estudio podría ser el análisis longitudinal más extenso del que se tenga registro. Conocer la variedad de manifestaciones y complicaciones presentadas permitirá al lector seleccionar el mejor método de tratamiento para cada caso.

Abstract: Introduction: Pycnodysostosis is a rare disease secondary to a mutation in gen 1q21 that codifies the cathepsin K, proteolitic enzyme implicated in the metabolism of osteonectin, osteopontin and type I colagen. Its global incidence is around 1-1.7 cases per million, without genre prevalences, it is clinically caracterized by short stature, craneal deformities, «bird's face¼ and bone fragility with pathological fractures tendency predominantly affecting long bones and occasionally vertebral pedicles. Radiologically is characterized by sclerous bones with permeable medular cannel. Despite there are numerous clinical reports on medical literature, just a litlle describe families with more than one afected member and its followship is usually short-term. Objective: To analize clinical evolution of these afected patients. Material and methods: A retrospective, descriptive, observational study was reelized in three patients with diagnosis of pycnodisostosis, between July 2006 and March 2016. Results: different affection forms of pycnodisostosis where observed, some of them, atipical, as for example spondilolisis and a escapule fracture in one patien. Conclusions: The present study could be the longest longitudinal report ever registered. By knowing the presented variety of manifestations and complications, the reader could select the best treatment method for each case.

Comparative evaluation of cathepsin K levels in gingival crevicular fluid among smoking and nonsmoking patients with chronic periodontitis

The aim of the study is to comparatively evaluate the levels of cathepsin K (CSTK) in gingival crevicular fluid (GCF) among smoking and nonsmoking patients with chronic periodontitis (CP). Materials and Methods: A total of 160 systemically healthy male patients were included in the study. Based on probing pocket depth, clinical attachment level, plaque index, and modified sulcular bleeding index, the patients were allotted into four groups: Group I - with forty subjects who were smokers with healthy periodontium, Group II - with forty nonsmoking subjects with healthy periodontium, Group III - forty patients who were smokers with CP, and Group IV - with forty nonsmoking CP patients. Those who claimed to have never smoked were recruited into the nonsmoker group, whereas subjects who reported smoking ≥10 cigarettes per day for more than 5 years were recruited into the smoker group. The GCF samples were collected using microcapillary pipettes and analyzed for levels of CSTK using enzyme-linked immunosorbent assay. Results: The GCF concentration of CSTK was expressed in pg/μl. The mean CSTK levels in the groups were Group I - 0.158 ± 0.043 pg/μl, Group II - 0.145 ± 0.026 pg/μl, Group III - 15.768 ± 12.40 pg/μl, and for Group IV - 11.59 ± 12.15 pg/μl, respectively. The levels of CSTK were statistically higher in Group III when compared with Group IV (P = 0.037) (P < 0.05). Conclusion: CSTK levels were significantly increased in smokers with CP than nonsmokers, suggesting a positive influence of smoking on CSTK which could possibly play a role in the increased susceptibility for osteoclastic bone destruction in smoker subjects.

Prenylated flavonoids from the roots of Artocarpus heterophyllus / 药学学报

Ten isoprenylated flavonoids were isolated from 95% ethanol extraction of Artocarpus heterophyllus, with a combination of various chromatographic approaches, including ODS, MCI, CHP-20 P, Sephadex LH-20 and high performance liquid chromatography. On the basis of physic-chemical characters and spectroscopic data analysis, these compounds were identified as artoheteroid E (1), cycloheterophyllin (2), artelastoxanthone (3), artoindonesianin Q (4), cudraflavone C (5), 8-(γ,γ-dimethylallyl)-5,2',4'-trihydroxy-7-methoxyflavone (6), kuwanon T (7), 6-(3-methylbut-2-enyl) apigenin (8), 5,7,2',4'-tetrahydroxy-6-(3-methylbut-3-enyl) flavone (9), albanin A (10). Among them, compound 1 is a new one, while compounds 2-4 were isolated for the first time from the plant of Artocarpus heterophyllus. All isolated compounds were screened for their inhibitory abilities against cathepsin K. Of them, compounds 3-5, 7 and 10 showed inhibitory effects with the IC50 values of 0.9, 1.6, 4.5, 24.5 and 63.5 μmol·L-1, respectively.

Study on exosite inhibitor of cathepsin K from Herba Ecliptae fractions / 药学学报

Cathepsin K (CTSK) is considered a critical pharmaceutical target in the treatment of osteoporosis. CTSK exerts proteolytic activities against regulatory proteins besides its collagenase function, which may account for some of the adverse reactions when blocked by active site-directed inhibitors. Exosite inhibitors that can discriminate between the therapeutic collagenase and other biological activities of CTSK specifically inhibit the collagenase activity of CTSK without interfering with the other proteolytic activities of the protease. Active recombinant CTSK was expressed in Pichia pastoris, and purified by n-butyl sepharose and SP sepharose column chromatography. Herba Ecliptae is a common traditional Chinese medicine in the treatment of bone diseases. Collagenase assay and benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin (Z-FR-MCA) substrate assay based on CTSK are applied to verify the exosite inhibitors. n-Butanol extract of Herba Ecliptae are the most active fraction and eclalbasaponin IX isolated from n-butanol fraction is the potential exosite inhibitor of CTSK.

An experimental study of effect of curcumin on improvementof bone microarchitecture and bone quality inhigh-fat-diet C57BL/6J mice and its association with cathepsin K / 中国药理学通报

Aim To investigate the effect of curcumin against high-fat-diet induced C57BL/6J mice bone changes and the correlation between the expression of cathepsin K and curcumin.Methods Curcumin treated C57BL/6J mice had been on high fat diet for 12 weeks.The HE, Alizarin red S staining and Safranin O/fast green staining of femur were employed to evaluate bone microstructure, bone metabolism and bone development.The expressions of cathepsin K were assessed by Western blot and immunohistochemical staining.Results Histopathological results showed that curcumin could improve the destruction of trabecular bone structure, cartilage development and bone calcification.Biomechanical results proved that curcumin could improve the bone strength of the type 2 diabetic mice induced by high fat.The results of immunohistochemistry and Western blot assay indicated that curcumin could significantly inhibit the expression of cathepsin K in bone tissues of mice.Conclusion Curcumin can increase bone strength, improve bone microstructure, and enhance the degree of bone calcification, which may be achieved by inhibiting the expression of cathepsin K.

Fracturas múltiples de huesos largos en una escolar portadora de picnodisostosis: Reporte de caso / Multiple long bone fractures in a child with pycnodysostosis: A case report

Las fracturas en edad pediátrica son una entidad importante para considerar. Hay enfermedades en que los huesos del niño se fracturan ante traumatismos de menor energía. La picnodisostosis es un tipo inusual de displasia cráneo-metafisaria autosómica recesiva, cuya primera manifestación clínica suele ser una fractura en hueso patológico. Se presenta a una paciente, caucásica, de 9 años de edad, con diagnóstico de picnodisostosis, que ingresó al hospital por fractura del fémur derecho, por un mecanismo de baja energía. Los estudios radiográficos mostraron fracturas del fémur bilateral, fractura proximal de la tibia izquierda y consolidación viciosa en antecurvatum. Esta rara enfermedad se diagnostica a edades tempranas por talla baja, por fracturas repetidas o por traumas de baja energía. Las opciones terapéuticas son limitadas, y no se ha desarrollado una cura definitiva. Es importante, ante un paciente pediátrico con rasgos dismórficos faciales y fracturas en hueso patológico, sospechar displasias óseas, tales como la picnodisostosis y sus diagnósticos diferenciales.

Fractures are an important entity to consider in pediatric patients. There are certain diseases in which bones fracture with a minimal trauma. Pycnodysostosis is an autosomal recessive unusual type of cráneo metaphyseal dysplasia, that presents frequently as fracture in a pathological bone. A 9 year old caucasian female, diagnosed with pycnodysostosis, was admitted with a right femur fracture as a result of a low energy trauma. Radiographic studies showed bilateral femur fractures, proximal fracture and non-union in antecurvatum of the left tibia. Pycnodysostosis is a rare disease, generally diagnosed at an early age by growth restriction, frequent fractures or fractures with low energy trauma. Therapy alternatives are limited, and no permanent cure has been developed. If a patient has dysmorphic facial features and fractures in a pathological bone, it is important to suspect bone dysplasia, such as pycnodysostosis and its differential diagnoses.

Pyknodysostosis (Rare Skeletal Defect): A Case Report.

Pyknodysostosis is a defective bone disease that is responsible in many bone deformities. We report a case with recurrent urti, growth retardation, facial dysmorphism, delayed eruption of teeth & inability to gain weight properly since childhood and successful treatment of the patient by supportive measures.

Emerging Therapies for Osteoporosis

Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients.

Pycnodysostosis with Multi-Segmental Spinal Canal Stenosis due to Ossification of the Yellow Ligament

Pycnodysostosis is an autosomal recessive disorder characterized by osteosclerosis, small stature, acro-osteolysis of the distal phalanges, loss of the mandibular angle, separated cranial sutures with open fontanels, and frequent fractures. One identified cause of the disease is reduced activity of the cysteine protease cathepsin K. A 48-year-old woman with a history of frequent fractures presented with a severe gait disturbance. Radiography, computed tomography, magnetic resonance imaging, and gene analysis were performed. Physical examination revealed open fontanels, and radiographs showed increased bone density. DNA sequence analysis revealed a deletion mutation of the cathepsin K gene. We diagnosed pycnodysostosis based on these findings. The magnetic resonance and computed tomography images demonstrated multilevel spinal canal stenosis due to ossification of the yellow ligament. We performed a laminectomy, and the patient's neurological signs and symptoms improved. To our knowledge, this is the first case of pycnodysostosis with ossification of the yellow ligament.

Peri-implant crevicular fluid levels of cathepsin-K, RANKL, and OPG around standard, short, and mini dental implants after prosthodontic loading

PURPOSE: Despite the high success rates of endosseous dental implants, their placement is restricted according to the height and volume of bone available. The use of short or mini dental implants could be one way to overcome this limitation. Thus, this study aimed to compare standard, short, and mini dental implants with regard to associated clinical parameters and peri-implant crevicular fluid (PICF) levels of cathepsin -K (CTSK), RANK ligand (RANKL), and osteoprotegerin (OPG), after prosthodontic loading. METHODS: A total of 78 non-submerged implants (Euroteknika, Aesthetica+2, Sallanches, France) were installed in 30 subjects (13 male, 17 female; range, 26-62 years) who visited the clinic of the Periodontology Department, Faculty of Dentistry, Selcuk University. Sampling and measurements were performed on the loading date (baseline) and 2, 14, and 90 days after loading. Assessment of the peri-implant status for the implant sites was performed using the pocket probing depth (PPD), modified plaque index, modified gingival index, modified sulcular bleeding index, and radiographic signs of bone loss. PICF samples collected from each implant were evaluated for CTSK, RANKL, and OPG levels using the ELISA method. Keratinized tissue and marginal bone loss (MBL) were also noted. RESULTS: Clinical parameters statistically significantly increased in each group but did not show statistical differences between groups without PPD. Although implant groups showed a higher MBL in the upper jaw, only the standard dental group demonstrated a statistically significant difference. At 90 days, the OPG: sRANKL ratio and total amounts of CTSK for each group did not differ from baseline. CONCLUSIONS: Within the limitations of this study, both short and mini dental implants were achieving the same outcomes as the standard dental implants in the early period after loading.

Increased Serum Cathepsin K in Patients with Coronary Artery Disease

PURPOSE: Cathepsin K is a potent collagenase implicated in human and animal atherosclerosis-based vascular remodeling. This study examined the hypothesis that serum CatK is associated with the prevalence of coronary artery disease (CAD). MATERIALS AND METHODS: Between January 2011 and December 2012, 256 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. A total of 129 age-matched subjects served as controls. RESULTS: The subjects' serum cathepsin K and high sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher serum cathepsin K levels compared to the controls (130.8+/-25.5 ng/mL vs. 86.9+/-25.5 ng/mL, p<0.001), and the patients with acute coronary syndrome had significantly higher serum cathepsin K levels compared to those with stable angina pectoris (137.1+/-26.9 ng/mL vs. 102.6+/-12.9 ng/mL, p<0.001). A linear regression analysis showed that overall, the cathepsin K levels were inversely correlated with the high-density lipoprotein levels (r=-0.29, p<0.01) and positively with hs-CRP levels (r=0.32, p<0.01). Multiple logistic regression analyses shows that cathepsin K levels were independent predictors of CAD (odds ratio, 1.76; 95% confidence interval, 1.12 to 1.56; p<0.01). CONCLUSION: These data indicated that elevated levels of cathepsin K are closely associated with the presence of CAD and that circulating cathepsin K serves a useful biomarker for CAD.