Roles of inflammatory cell infiltrate in periprosthetic osteolysis.

Classically, particle-induced periprosthetic osteolysis at the implant-bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+) coexisting with CD68+/TRAP- multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.

Review of the Mechanism of Action and Use of Bisphosphonates in Horses.

Bisphosphonates are a group of drugs that can reduce bone resorption by incorporating into the crystal structure of exposed hydroxyapatite where they are taken up by osteoclasts. Bisphosphonates have several other mechanisms of action including reducing pain and inflammation and altering macrophage function. There are two types of bisphosphonates-nitrogenous and non-nitrogenous, the latter of which is used in horses. This article provides a literature-based review of the proposed mechanisms of action and therapeutic uses of bisphosphonates including a brief review of bone response to disease. A review of the literature available in horses including safety data and current rules and regulations is also provided.

Fracture healing, the diamond concept under the scope: hydroxyapatite and the hexagon.

Bone healing after a fracture has many intercalated steps that depend on the host, type of injury, and often the orthopedist. The diamond concept since 2007 has outlined 4 main facets that have to be considered as a model by the treating surgeon at the time of injury and when nonunion develops: osteogenic cells, osteoconductive scaffolds, osteoinduction, and the biomechanical environment. All of these foment fracture healing in optimal circumstances. Yet, this work proposes other facets, such as osteoimmunology and vascularity, to be considered as well in the model. These are as important as the original four, though their correlation to the original work has been less noted until more recent literature. The mindset of the orthopedist must thoroughly analyze all these facets and many more when dealing with nonunion. This work presents, probably the most significant ones, parting from the original 4-corner diamond model and expanding it to a more representative hexagon integrated model. Metaphorically, just like the strongest inorganic constituent of the bone: hydroxyapatite.

Hay múltiples pasos intercalados en la consolidación de la fractura que dependen del paciente, el tipo de fractura y frecuentemente del ortopedista. Desde su introducción en el año 2007, el concepto del diamante ha delineado 4 facetas o aristas principales que se han de tener en cuenta por el ortopedista en el momento de la lesión y cuando la no-unión de fractura ocurre: células osteogénicas, matrices osteocunductivas, osteoinducción, y el ambiente biomecánico. Otras facetas para tener en cuenta, no menos importantes, son la osteoimmunología y la vascularidad. Estas son tan importantes como las 4 facetas originales, pero la correlación entre las mismas ha sido poco notada o integrada hasta ahora. El ortopedista tratante debe analizar todas ellas en profundidad, especialmente cuando se trata de una no-unión. Este trabajo presenta las más significantes, partiendo del modelo original del diamante de 4 facetas hacia uno más representativo e integrado como el hexágono. Metafóricamente, como el elemento inorgánico más abundante y fuerte en el hueso: la hidroxiapatita.

Fracture healing, the diamond concept under the scope: Hydroxyapatite and the hexagon / Consolidación de fractura, una mirada al concepto diamante: Hidroxiapatita y el hexágono

Abstract Bone healing after a fracture has many intercalated steps that depend on the host, type of injury, and often the orthopedist. The diamond concept since 2007 has outlined 4 main facets that have to be considered as a model by the treating surgeon at the time of injury and when nonunion develops: osteogenic cells, osteoconductive scaffolds, osteoinduction, and the biomechanical environment. All of these foment fracture healing in optimal circumstances. Yet, this work proposes other facets, such as osteoimmunology and vascularity, to be considered as well in the model. These are as important as the original four, though their correlation to the original work has been less noted until more recent literature. The mindset of the orthopedist must thoroughly analyze all these facets and many more when dealing with nonunion. This work presents, probably the most sig nificant ones, parting from the original 4-corner diamond model and expanding it to a more representative hexagon integrated model. Metaphorically, just like the strongest inorganic constituent of the bone: hydroxyapatite.

Resumen Hay múltiples pasos intercalados en la consolidación de la fractura que dependen del paciente, el tipo de fractura y frecuentemente del ortopedista. Desde su introducción en el año 2007, el concepto del diamante ha delineado 4 facetas o aristas principales que se han de tener en cuenta por el ortopedista en el momento de la lesión y cuando la no-unión de fractura ocurre: células osteogénicas, matrices osteocunductivas, osteoinducción, y el ambiente biomecánico. Otras facetas para tener en cuenta, no menos importantes, son la osteoimmunología y la vascularidad. Estas son tan importantes como las 4 facetas originales, pero la correlación entre las mismas ha sido poco notada o integrada hasta ahora. El ortopedista tratante debe analizar todas ellas en profundidad, especialmente cuando se trata de una no-unión. Este trabajo presenta las más significantes, partiendo del modelo original del diamante de 4 facetas hacia uno más representativo e integrado como el hexágono. Metafóricamente, como el elemento inorgánico más abundante y fuerte en el hueso: la hidroxiapatita.

Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern in the Osteoimmunology Arena.

Cellular senescence is a biological process triggered in response to time-accumulated DNA damage, which prioritizes cell survival over cell function. Particularly, senescent T lymphocytes can be generated prematurely during chronic inflammatory diseases regardless of chronological aging. These senescent T lymphocytes are characterized by the loss of CD28 expression, a co-stimulatory receptor that mediates antigen presentation and effective T-cell activation. An increased number of premature senescent CD4+CD28- T lymphocytes has been frequently observed in osteolytic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, osteopenia, osteoporosis, and osteomyelitis. Indeed, CD4+CD28- T lymphocytes produce higher levels of osteoclastogenic molecular mediators directly related to pathologic bone loss, such as tumor necrosis factor (TNF)-α, interleukin (IL)-17A, and receptor-activator of nuclear factor κB ligand (RANKL), as compared with regular CD4+CD28+ T lymphocytes. In addition, premature senescent CD8+CD28- T lymphocytes have been negatively associated with bone healing and regeneration by inhibiting osteoblast differentiation and mesenchymal stromal cell survival. Therefore, accumulated evidence supports the role of senescent T lymphocytes in osteoimmunology. Moreover, premature senescence of T-cells seems to be associated with the functional imbalance between the osteolytic T-helper type-17 (Th17) and bone protective T regulatory (Treg) lymphocytes, as well as the phenotypic instability of Treg lymphocytes responsible for its trans-differentiation into RANKL-producing exFoxp3Th17 cells, a key cellular phenomenon directly related to bone loss. Herein, we present a framework for the understanding of the pathogenic characteristics of T lymphocytes with a premature senescent phenotype; and particularly, we revise and discuss their role in the osteoimmunology of osteolytic diseases.

Osteoimmunology drives dental implant osseointegration: A new paradigm for implant dentistry.

There is a complex interaction between titanium dental implants, bone, and the immune system. Among them, specific immune cells, macrophages play a crucial role in the osseointegration dynamics. Infiltrating macrophages and resident macrophages (osteomacs) contribute to achieving an early pro-regenerative peri-implant environment. Also, multinucleated giant cells (MNGCs) in the bone-implant interface and their polarization ability, maintain a peri-implant immunological balance to preserve osseointegration integrity. However, dental implants can display cumulative levels of antigens (ions, nano and microparticles and bacterial antigens) at the implant-tissue interface activating an immune-inflammatory response. If the inflammation is not resolved or reactivated due to the stress signals and the immunogenicity of elements present, this could lead implants to aseptic loosening, infections, and subsequent bone loss. Therefore, to maintain osseointegration and prevent bone loss of implants, a better understanding of the osteoimmunology of the peri-implant environment would lead to the development of new therapeutic approaches. In this line, depicting osteoimmunological mechanisms, we discuss immunomodulatory strategies to improve and preserve a long-term functional integration between dental implants and the human body. Scientific field of dental science: implant dentistry.

Macrophage Polarization and Alveolar Bone Healing Outcome: Despite a Significant M2 Polarizing Effect, VIP and PACAP Treatments Present a Minor Impact in Alveolar Bone Healing in Homeostatic Conditions.

Host inflammatory immune response comprises an essential element of the bone healing process, where M2 polarization allegedly contributes to a favorable healing outcome. In this context, immunoregulatory molecules that modulate host response, including macrophage polarization, are considered potential targets for improving bone healing. This study aims to evaluate the role of the immunoregulatory molecules VIP (Vasoactive intestinal peptide) and PACAP (Pituitary adenylate cyclase activating polypeptide), which was previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups were submitted to tooth extraction and maintained under control conditions or treated with VIP or PACAP were evaluated by microtomographic (µCT), histomorphometric, immunohistochemical, and molecular analysis at 0, 3, 7, and 14 days to quantify tissue healing and host response indicators at the healing site. Gene expression analysis demonstrates the effectiveness of VIP or PACAP in modulating host response, evidenced by the early dominance of an M2-type response, which was paralleled by a significant increase in M2 (CD206+) in treated groups. However, despite the marked effect of M1/M2 balance in the healing sites, the histomorphometric analysis does not reveal an equivalent/corresponding modulation of the healing process. µCT reveals a slight increase in bone matrix volume and the trabecular thickness number in the PACAP group, while histomorphometric analyzes reveal a slight increase in the VIP group, both at a 14-d time-point; despite the increased expression of osteogenic factors, osteoblastic differentiation, activity, and maturation markers in both VIP and PACAP groups. Interestingly, a lower number of VIP and PACAP immunolabeled cells were observed in the treated groups, suggesting a reduction in endogenous production. In conclusion, while both VIP and PACAP treatments presented a significant immunomodulatory effect with potential for increased healing, no major changes were observed in bone healing outcome, suggesting that the signals required for bone healing under homeostatic conditions are already optimal, and additional signals do not improve an already optimal process. Further studies are required to elucidate the role of macrophage polarization in the bone healing process.

Inflammatory response and macrophage polarization using different physicochemical biomaterials for oral and maxillofacial reconstruction.

Knowledge about the action of immune system in the recognition of biomaterials has been extremely helpful when it comes about understanding host response and biomaterials' fate in human body. This study aimed to investigate inflammatory response and macrophage polarization during bone healing process of rat's calvaria critical defects using different bone materials in order to evaluate their influence on bone repair and on the quality of the newly formed bone tissue. Eighty male albinus Wistar rats underwent surgical procedure for the confectioning of a 5-mm diameter bone defect in their right parietal bone, and divided in four groups (n = 20 each), according the biomaterial: AG - Control, particulate intramembranous autogenous bone graft, HA/TCP - particulate biphasic calcium phosphate with HA/TCP (60/40), DBB - particulate deproteinized bovine bone, VC - particulate bioactive vitroceramic. After 3, 7, 21, and 45 days, the specimens were removed and prepared for microcomputed tomography (microCT), light and polarized microscopy, immunohistochemical analysis, and histomorphometry. No significant differences were detected considering percentage of leukocytes among the groups and periods, as well as in relation to immunolabeling for inflammatory (M1) and reparative (M2) macrophages. However, immunolabeling for bone marker indicated a delayed osteoblast differentiation in VC group, resulting in a decrease in mineralized bone matrix parameters in this group, revealed by microCT. In addition, AG and HA/TCP presented a satisfactory bone collagenous content. Despite the distinct origins and physicochemical properties of the tested biomaterials, they presented similar immune-inflammatory responses in the present experimental model, influencing bone-related proteins and bone quality, which must be considered according to their use.

HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice.

The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome.

CCR2 Contributes to F4/80+ Cells Migration Along Intramembranous Bone Healing in Maxilla, but Its Deficiency Does Not Critically Affect the Healing Outcome.

Bone healing depends of a transient inflammatory response, involving selective migration of leukocytes under the control of chemokine system. CCR2 has been regarded as an essential receptor for macrophage recruitment to inflammation and healing sites, but its role in the intramembranous bone healing on craniofacial region remains unknown. Therefore, we investigated the role of CCR2 on F4/80+ cells migration and its consequences to the intramembranous healing outcome. C57BL/6 wild-type (WT) and CCR2KO mice were subjected to upper right incisor extraction, followed by micro-computed tomography, histological, immunological, and molecular analysis along experimental periods. CCR2 was associated with F4/80+ cells influx to the intramembranous bone healing in WT mice, and CCR2+ cells presented a kinetics similar to F4/80+ and CCR5+ cells. By contrast, F4/80+ and CCR5+ cells were significantly reduced in CCR2KO mice. The absence of CCR2 did not cause major microscopic changes in healing parameters, while molecular analysis demonstrated differential genes expression of several molecules between CCR2KO and WT mice. The mRNA expression of TGFB1, RUNX2, and mesenchymal stem cells markers (CXCL12, CD106, OCT4, NANOG, and CD146) was decreased in CCR2KO mice, while IL6, CXCR1, RANKL, and ECM markers (MMP1, 2, 9, and Col1a2) were significantly increased in different periods. Finally, immunofluorescence and FACS revealed that F4/80+ cells are positive for both CCR2 and CCR5, suggesting that CCR5 may account for the remaining migration of the F4/80+ cells in CCR2KO mice. In summary, these results indicate that CCR2+ cells play a primary role in F4/80+ cells migration along healing in intramembranous bones, but its deficiency does not critically impact healing outcome.

Polymorphisms in key bone modulator cytokines genes influence bisphosphonates therapy in postmenopausal women.

Osteoporosis is a multifactorial and debilitating disease resulting from decreased bone mineral density (BMD) and loss of tissue microarchitecture. Ineffective therapies may lead to bone fractures and subsequent death. Single nucleotide polymorphisms (SNPs) in key immune regulator genes have been associated with therapeutic response to bisphosphonates, which are the first therapeutic line of choice for osteoporosis. However, cytokine pathways and their relation with therapeutic adhesion remain to be fully elucidated. Aimed at better understanding these processes, we investigated the response to bisphosphonate therapy in postmenopausal women and four SNPs in key proinflammatory cytokines genes: IL23R +2284 (C>A) (rs10889677), IL17A +672 (G>A) (rs7747909), IL12B +1188 (T>G) (rs3212227) and INF-γ -1616 (G>A) (rs2069705). A total of 69 patients treated with bisphosphonate were followed for a period of 1 up to 4 years, genotyped and compared according to their changes in bone mineral density (BMD) and level of biochemical markers during their treatment. The INF-γ -1616 G/G associated with increased BMD values in femoral neck (GG/AA, p = 0.016) and decreased BMD values in total hip (GG/GA, p = 0.019; GG/AA, p = 0.011). In relation to biochemical markers, INF-γ -1616 SNP associated with increased alkaline phosphatase (GG/AA; p < 0.0001) and parathyroid hormone levels (AA/GA; p = 0.017). Vitamin D values changes were related to IL17A +672 (GG/GA, p = 0.034) and to IL12B +1188 (TT/TG, p = 0.046) SNPs. Besides, significant differences in changes of calcium levels correlated with IL23R +2284 (CC/CA, p = 0.016) genotypes. Altogether, we suggest that these polymorphisms may play an important role for therapeutic decisions in osteoporosis treatment.

Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology.

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood. On the other hand it is well known that inflammation is a key player in GD pathology. In this work, we revealed increased levels of the proinflammatory CD14(+)CD16(+) monocyte subset and increased inflammatory cytokine production by monocytes and T cells in the circulation of GD patients. We showed increased levels of osteoclast precursors in PBMC from patients and a higher expression of RANKL in the surface of T cells. PBMC from patients presented higher osteoclast differentiation compared to healthy controls when cultured in the presence of M-CSF alone or in combination with RANKL. In vitro treatment with Velaglucerase reduced osteoclast levels to control levels. On the other hand THP-1 derived osteoclast precursors cultured in the presence of conditioned media from PBMC of GD patients presented higher differentiation to active osteoclasts. This induction involved TNF-α and RANKL.

Host response mechanisms in periodontal diseases

Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that presents a significantly host immune and inflammatory response to the microbial challenge that determine of susceptibility to develop the destructive/progressive periodontitis under the influence of multiple behavioral, environmental and genetic factors.

IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis.

Inflammatory bone resorption is a hallmark of periodontitis, and Tregs and Th2 cells are independently associated with disease progression attenuation. In this study, we employed an infection-triggered inflammatory osteolysis model to investigate the mechanisms underlying Treg and Th2 cell migration and the impact on disease outcome. Aggregatibacter actinomycetemcomitans-infected C57Bl/6 (wild-type [WT]) mice develop an intense inflammatory reaction and alveolar bone resorption, and Treg and Th2 cell migration is temporally associated with disease progression attenuation. Tregs extracted from the lesions preferentially express CCR4 and CCR8, whereas Th2 cells express CCR3, CCR4, and CCR8. The absence of CCR5 and CCR8 did not significantly impact the migration of Tregs and Th2 cells or affect the disease outcome. CCR4KO mice presented a minor reduction in Th2 cells in parallel with major impairment of Treg migration, which was associated with increased inflammatory bone loss and higher proinflammatory and osteoclastogenic cytokine levels. The blockade of the CCR4 ligand CCL22 in WT mice resulted in an increased inflammatory bone loss phenotype similar to that in the CCR4KO strain. Adoptive transfer of CCR4(+) Tregs to the CCR4KO strain revert the increased disease phenotype to WT mice-like levels; also, the in situ production of CCL22 in the lesions is mandatory for Tregs migration and the consequent bone loss arrest. The local release of exogenous CCL22 provided by poly(lactic-co-glycolic acid) (PLGA) microparticles promotes migration of Tregs and disease arrest in the absence of endogenous CCL22 in the IL-4KO strain, characterized by the lack of endogenous CCL22 production, defective migration of Tregs, and exacerbated bone loss. In summary, our results show that the IL-4/CCL22/CCR4 axis is involved in the migration of Tregs to osteolytic lesion sites, and attenuates development of lesions by inhibiting inflammatory migration and the production of proinflammatory and osteoclastogenic mediators.

NOD2 contributes to Porphyromonas gingivalis-induced bone resorption.

The NOD-like receptors are cytoplasmic proteins that sense microbial by-products released by invasive bacteria. Although NOD1 and NOD2 are functionally expressed in cells from oral tissues and play a role triggering immune responses, the role of NOD2 receptor in the bone resorption and in the modulation of osteoclastogenesis is still unclear. We show that in an experimental model of periodontitis with Porphyromonas gingivalis W83, NOD2(-/-) mice showed lower bone resorption when compared to wild type. Quantitative polymerase chain reaction analysis revealed that wild-type infected mice showed an elevated RANKL/OPG ratio when compared to NOD2(-/-) infected mice. Moreover, the expression of 2 osteoclast activity markers-cathepsin K and matrix metalloproteinase 9-was significantly lower in gingival tissue from NOD2(-/-) infected mice compared to WT infected ones. The in vitro study reported an increase in the expression of the NOD2 receptor 24 hr after stimulation of hematopoietic bone marrow cells with M-CSF and RANKL. We also evaluated the effect of direct activation of NOD2 receptor on osteoclastogenesis, by the activation of this receptor in preosteoclasts culture, with different concentrations of muramyl dipeptide. The results show no difference in the number of TRAP-positive cells. Although it did not alter the osteoclasts differentiation, the activation of NOD2 receptor led to a significant increase of cathepsin K expression. We confirm that this enzyme was active, since the osteoclasts resorption capacity was enhanced by muramyl dipeptide stimulation, evaluated in osteoassay plate. These results show that the lack of NOD2 receptor impairs the bone resorption, suggesting that NOD2 receptor could contribute to the progression of bone resorption in experimental model of periodontitis. The stimulation of NOD2 by its agonist, muramyl dipeptide, did not affect osteoclastogenesis, but it does favor the bone resorption capacity identified by increased osteoclast activity.

Principios básicos de la osteoinmunología en las enfermedades reumáticas / Basic principles of osteoimmunology in rheumatic diseases

El estudio de la inmunología ósea va adquiriendo cada vez mayor relevancia en la comprensión de las enfermedades reumatológicas y sus potenciales manejos. El conocimiento de la estructura y función ósea de los distintos tipos de tejidos óseos, así como las vías clave involucradas en los procesos de osificación y remodelación ósea, son hoy en día puntos fundamentales para entender y proponer nuevos tratamientos. Mediante el estudio de la osteoinmunología se ha logrado explicar procesos característicos de las enfermedades reumatológicas, como lo son las erosiones óseas yuxta-articulares, la osteoporosis periarticular y sistémica, además de la neoformación de hueso que ocurre en enfermedades como la espondilitis anquilosante o la osteoartritis. A continuación se expone una revisión detallada de los conocimientos actuales en osteoinmunología.

The study of osteoimmunology is gaining increasing importance in the understanding of rheumatic diseases and their potential treatments. The knowledge of the bone structure and function of the different types of bone tissues, as well as the key pathways involved in the processes of ossification and bone remodeling, are now key points in the understanding and the development of new treatments. The osteoimmunology has explained different processes that are characteristic in the rheumatic diseases, such as juxta-articular bone erosions, periarticular and systemic osteoporosis, as well as the new bone formation that occurs in diseases such ankylosing spondylitis or osteoarthritis. In this presentation, it will be presented a detailed review of the current knowledge in osteoimmunology.

Osteoimunologia aplicada às reconstruções maxilofaciais: [revisão] / Osteoimmunology applied to maxillofacial reconstruction: [review]

Esta revisão de literatura teve por objetivo discutir os aspectos atuais da osteoimunologia aplicada às reconstruções maxilofaciais. As reabilitações maxilares por implantes podem demandar enxertia óssea para prévia adequação do rebordo à colocação do implante. Os enxertos ósseos alógenos têm sido introduzidos nesse protocolo para evitar cirurgia numa segunda área. A criopreservação figura como um método importante para diminuir a antigenicidade do tecido, mas outras técnicas podem ser exemplificadas como a esterilização por radiação gama ou óxido de etileno. A imunologia participa do processo de incorporação ou de rejeição dos enxertos ósseos incrementando sua absorção. Diversas moléculas, como as interleucinas, o ligante do receptor ativador do fator nuclear-κβ (RANKL), o fator nuclear de células T ativadas (NFAT), o fator estimulador de colônias de macrófagos (M-CSF), o fator de células B jovens (EBF-2) e a osteoprotegerina estabelecem a relação entre as células imunológicas e o metabolismo do osso enxertado. As evidências obtidas da literatura permitem inferir que o osso alógeno congelado é um bom material para aposição dos maxilares por não induzir rejeição imunológica.

This literature review aimed to discuss some current aspects related to osteoimmunology applied to maxillofacial reconstruction. Maxillary rehabilitation with implants may demand bone grafting before implant placement in the alveolar ridge. Allografts have been introduced to prevent surgery in a secondary area. Cryopreservation is an important method to decrease tissue antigenicity, but other techniques can also be used such as sterilization by gamma radiation or ethylene oxide. Immunology may participate in the incorporation or rejection process of bone grafts by increasing bone resorption. Several molecules, such as interleukins, receptor activators of nuclear factor κβ ligand RANKL, nuclear factor of activated T cells (NFAT), macrophage-colony stimulating factor (M-CSF), early B cell factor (EBF-2), and osteopontegrin establish the relation between immunological cells and bone graft metabolism. Evidences from the literature suggest that frozen allogenic bone may be a good material for jaw onlay grafts since they do not induce immunological rejection.