Interactions between bone and immune systems: A focus on the role of inflammation in bone resorption and fracture healing

Functional interactions between the immune system and bone tissues are reflected in a number of cytokines, chemokines, hormones and other mediators regulating the functions of both bone and immune cells. Investigations of the mechanisms of those interactions have become important for the understanding of the pathogeneses of diseases like inflammatory arthritis, inflammatory bowel disease, periodontal disease and osteoporosis. This review first addresses the roles of the inflammatory mediators and mechanisms by which they cause inflammation-induced bone loss. In the second part of the review we stress the importance of proinflammatory mediators for normal fracture healing. Defective bone remodeling underlying different pathological processes may be caused by disturbed differentiation and function of either osteoclast or osteoblast lineage cells. Understanding of the mechanisms governing enhanced differentiation and activation of osteoclast progenitors in the inflammatory conditions on the one hand, and the role of inflammation in the recruitment and differentiation of multipotent progenitors into the skeletal lineage during the fracture healing on the other hand is a critical first step in developing interventions that modulate bone regeneration processes and in designing novel pharmacological strategies

Frequency of Bacetrial Content Finding in Persistant Periapical Lesions

Ciljevi: Svrha ovoga rada bila je odrediti postotak perzistentnih apikalnih lezija pozitivnih na bakterijske nukleinske kiseline, zatim s pomoću lančane reakcije polimeraze detektirati mikroorganizme u periapikalnim lezijama koje je teško kultivirati te ih povezati s endodontskim neuspjehom, kliničkih simptomima i dijabetesom. Materijali i postupci: Uzorci perzistentnih apikalnih lezija skupljani su tijekom apikotomije. Bakterijska ubikvitarna početnica 16S rRNK rabljena je za otkrivanje 16S ribosomskog RNK u 36 uzoraka. PCR usmjeren na pojedine vrste proveden je s pomoću početnica za 16S rRNK gene Prevotelle nigrescens, Pseudoramibactera alactolyticusa i Propionobacterium propionicum. Rezultati: Šest uzoraka (16,67 %) bilo je pozitivno na bakterijski ribosomski RNK. Pseudoramibacter alactolyticus detektiran je u trima uzorcima. Propionibacterium propionicum i Prevotella nigrescens detektirani su svaki u po jednom uzorku. Prevalencija infekcije ovih lezija P. intermedia, P. propionicum i P. alactolyticusom niska je. Provedeno istraživanje nije dalo dostatne podatke o povezanosti ekstraradikularne infekcije s dijabetesom melitusom i kliničkim simptomima. Zaključci: Apikalne lezije koje perzistiraju nakon endodontskog liječenja mogu, uz Actinomyces i Propionicum species, sadržavati i druge mikroorganizme.Objectives: To determine the percentage of persistant apical lesions positive for bacterial nucleic acids, to detect microorganisms difficult to cultivate in persistant apical lesions by PCR and relate them to endodontic failure, clinical symptoms and diabetes mellitus. Materials and methods: The samples of persistent apical lesions were collected during apicoectomy. Bacterial ubiquitous primer 16S rRNA was used to detect 16S ribosomal RNA in 36 samples. A species–specific PCR was performed with primers targeted to the bacterial 16S rRNA genes of Prevotella Nigrescens, Pseudoramibacter alactolyticus, and Propionobacterium propionicum. Results: Six samples (16.67%) were positive for bacterial ribosomal RNA. Pseudoramibacter alactolyticus was detected in three samples. Propionibacterium propionicum and Prevotella nigrescens were detected in one sample each. The prevalence of infection of such lesions with P. intermedia, P. propionicum and P. alactolyticus is low. Conslusion: The study we conducted gave insufficient data about extraradicular infection and its connection with diabetes mellitus and clinical symptoms. Conclusions: Apical lesions persisting after endodontic treatment could harbor microorganisms other than Actinomyces and Propionicum species

Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.2881+1G>A variant of the COL4A3gene, that is considered disease-causing. All patients were from the continental or island part of Croatia. Clinical, laboratory, and histopathological data collected from the medical records were analyzed and compared to understand the clinical course and prognosis of the affected patients. At the time of biopsy or first clinical evaluation, the mean age was 31 years (median: 35 years; range: 1 – 72 years). Hematuria was present in 33 patients (97.1%) and 19 (55.9%) patients had proteinuria. There were 6 (17.6%) patients with hearing loss, 4 (11.8%) with ocular lesions, and 11 (32.4%) with hypertension. Twenty-three (67.6%) patients had proteinuria at follow-up, and 5 (14.7%) patients with the median age of 48 years (range: 27-55) progressed to kidney failure, started dialysis, or underwent kidney transplantation. Of the 13 patients who underwent kidney biopsy, 4 (30.8%) developed focal segmental glomerulosclerosis (FSGS), and 8 (66.7%) showed lamellation of the GBM, including all patients with FSGS. It is essential to conduct a detailed analysis of each collagen type IV genetic variant to optimize the prognosis and therapeutic approach for affected patients

Bariatric surgery: evidence-based practical recommendations

[Resumen] La obesidad mórbida es, habitualmente, refractaria a los tratamientos convencionales, por lo que la modificación de hábitos dietéticos y de actividad física y/o el uso de fármacos consiguen pérdidas de peso parciales con habitual recuperación posterior. La cirugía bariátrica constituye una opción terapéutica para los casos de obesidad con elevado índice de masa corporal (IMC) asociada a comorbilidades, con buenos resultados a corto y largo plazo. El Grupo de Trabajo sobre Obesidad de la Sociedad Española de Endocrinología y Nutrición (GOSEEN) ha elaborado un documento con recomendaciones prácticas basadas en la evidencia para el tratamiento quirúrgico de la obesidad. La revisión se estructura en 3 partes. En la primera se definen los conceptos de obesidad y comorbilidades asociadas, los tratamientos médicos y sus resultados, las indicaciones y contraindicaciones para el tratamiento quirúrgico con los criterios de selección de los pacientes, el manejo pre y perioperatorio y la valoración de grupos especiales, como adolescentes y personas de edad avanzada. En la segunda parte se describen las distintas técnicas quirúrgicas, las vías de acceso y los resultados comparativos, las complicaciones tanto a corto como a largo plazo, la repercusión de la pérdida ponderal sobre las comorbilidades y los criterios para evaluar la efectividad de la cirugía. En la tercera parte se desarrolla el seguimiento postoperatorio, el control dietético en fases tempranas y más tardías tras la cirugía, y el calendario de control médico y analítico con la suplementación de los distintos macro y micronutrientes en función de la técnica quirúrgica empleada. Se incluye un apartado final sobre gestación y cirugía bariátrica, así como tablas y gráficos complementarios al texto desarrollado. La cirugía bariátrica sigue siendo un tratamiento discutido para la obesidad, pero los resultados en la corrección del exceso ponderal con mejoría en las patologías asociadas y en la calidad de vida confirman que puede ser el tratamiento de elección en pacientes seleccionados, con la técnica quirúrgica apropiada y con un correcto control pre y postoperatorio.[Abstract] Morbid obesity is usually refractory to conventional treatments. Consequently, weight that is lost by modifying diet and exercise and/or the use of drugs is usually later regained. Bariatric surgery constitutes a therapeutic option in obese patients with a high body mass index associated with comorbidities and achieves good results in both the short and the long term. The Obesity Working Group of the Spanish Society of Endocrinology and Nutrition has produced a document with practical, evidencebased recommendations for the surgical treatment of obesity. The review is structured in three parts. The first part defines the concepts of obesity and associated comorbidities, medical treatments, their results, and the indications and contraindications for surgical treatment, as well as the criteria for patient selection, pre- and perisurgical management, and assessment of special groups such as adolescents and the elderly. The second part discusses the different surgical techniques, approaches and comparative results, short- and long-term complications, the repercussions of weight loss on comorbidities, and the criteria for assessing the effectiveness of surgery. The third part discusses postsurgical follow-up, dietary control in the early and subsequent stages after surgery and the schedule for medical and laboratory follow-up, together with the different macro- and micronutrient supplements that should be used depending on the surgical technique employed. A final section is included on pregnancy and bariatric surgery, as well as tables and figures that complement the text. Although bariatric surgery continues to be a questionable treatment for obesity, the results correcting excess weight, with improvements in associated comorbidities and in quality of life, confirm that this option could be the treatment of choice in selected patients when the appropriate surgical technique and correct preand postoperative follow-up are employed

Effect of induced hematopoiesis on osteoclast differentiation and activity in mice

Osteoklasti su komponenta hematopoetske niše koštane srži, no njihova uloga u regulaciji hematopoeze nije dovoljno istražena i dosadašnji rezultati su proturječni. Istražili smo utjecaj potaknute hematopoeze nakon akutnog i kroničnog gubitka krvi na diferencijaciju i aktivnost mišjih osteoklasta. U modelu akutnog gubitka krvi naglasak smo stavili na preteče osteoklasta i izražaj gena uključenih u osteoklastogenezu te potencijal stanica koštane srži da se u in vitro uvjetima diferenciraju u koštane stanice. U modelu kroničnog gubitka krvi smo istražili učinak na aktivnost koštanih stanica odnosno koštanu pregradnju. Modelom akutnog gubitka krvi smo pokazali da potaknuta hematopoeza ne utječe na broj preteča osteoklasta, ali da potiče njihovo sazrijevanje. Model kroničnog gubitka krvi je pokazao da dugoročan gubitak krvi nema značajnog utjecaja na aktivnost osteoklasta i pregradnju trabekularne kosti. Rezultati su pokazali da krvarenje ne potiče aktivnost osteoklasta i koštanu razgradnju kako bi stvorili dodatan prostor za koštanu srž.Osteoclasts are components of hematopoietic bone marrow niche, but their role as hematopoietic contributors are still controversial. We aimed to investigate whether an acute and chronic blood loss and the consequent intense hematopoiesis would affect osteoclast differentiation and activity in mice. In the model of acute blood loss research was focused on specific subpopulations of osteoclast precursors, expression of osteoclastogenesis- and osteoblastogenesis-related genes and the potential of bone marrow cells to form osteoclast-like cells in vitro, while in the model of chronic blood loss on bone cells activity in vivo. There were no significant changes of cells with high osteoclastogenic potential, but we observed promoted osteoclast maturation following acute blood loss. Chronic blood loss had no effect on osteoclast activity and remodeling of trabecular bone. Our data demonstrate that blood loss does not promote osteoclast activity and osteoresorption to provide additional space for bone marrow

Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment

Osteoclasts are components of hematopoietic stem cell (HSC) niches, but their role as contributors to the HSC homeostasis and release are still controversial. We aimed to investigate whether an acute blood loss of 10% of total blood content, along with the consequent intense hematopoiesis, would affect osteoclast differentiation and activity. Isolated peripheral blood, spleen, and bone marrow (BM) cells from bones of hind limbs were investigated for the presence of specific subpopulations of osteoclast precursors: B220(-)CD3(-)NK1.1(-)CD11b(-/low)CD115(+)CD117(+) cells in BM, and B220(-)CD3(-)NK1.1(-)Gr-1(-)CD11b(+)CD115(+) cells in peripheral blood and spleen as well as the receptor activator of nuclear factor κ-B(+) cycle-arrested quiescent osteoclast precursors. Expression of osteoclastogenesis-related genes CD115, receptor activator of nuclear factor κ-B, and cathepsin K, the potential of BM cells to form osteoclast-like cells in vitro, and osteoclast activity in vivo were also evaluated. We observed an increase in spleen cellularity and myelopoiesis during week 1 following blood loss, without any significant effects on BM cellularity or BM myeloid precursors, including cells with high osteoclastogenic potential. However, at 1 week postbleeding, hematopoiesis significantly promoted the expression of cathepsin K, interleukin-34, and bone morphogenetic protein-6. Quiescent osteoclast precursors increased significantly in spleen 2 days following bleeding, whereas osteoclast activity remained unchanged up to 2 weeks postbleeding. Osteoclast-dependent B-cell differentiation was affected at the pre-B stage of maturation in BM, whereas the Lin(-)Sca-1(+)c-kit(+) population expanded in BM and spleen after 2 days postbleeding. Our data demonstrate that an acute blood loss promotes differentiation and maturation of osteoclasts at 1 week but does not enhance osteoresorption at 2 weeks postbleeding. Our data also identify osteoclast differentiation as a consequent and important event in establishing HSC homeostasis following hematopoietic stress

Interactions between bone and immune systems: A focus on the role of inflammation in bone resorption and fracture healing

Functional interactions between the immune system and bone tissues are reflected in a number of cytokines, chemokines, hormones and other mediators regulating the functions of both bone and immune cells. Investigations of the mechanisms of those interactions have become important for the understanding of the pathogeneses of diseases like inflammatory arthritis, inflammatory bowel disease, periodontal disease and osteoporosis. This review first addresses the roles of the inflammatory mediators and mechanisms by which they cause inflammation-induced bone loss. In the second part of the review we stress the importance of proinflammatory mediators for normal fracture healing. Defective bone remodeling underlying different pathological processes may be caused by disturbed differentiation and function of either osteoclast or osteoblast lineage cells. Understanding of the mechanisms governing enhanced differentiation and activation of osteoclast progenitors in the inflammatory conditions on the one hand, and the role of inflammation in the recruitment and differentiation of multipotent progenitors into the skeletal lineage during the fracture healing on the other hand is a critical first step in developing interventions that modulate bone regeneration processes and in designing novel pharmacological strategies