Bone Tumors: Types and Treatments

The tumors associated with bone are mostly of mesenchymal origin and contribute to approximately 1% of all the known tumors. These could be primary/benign tumors (that originate in the bone), secondary tumors (that originate in some other tissue/organ and metastasize to the bone), or malignant primary bone tumors (that originate in bone and metastasize to distant tissue). These tumors are majorly due to defects in the regulation of tumor suppressor genes and oncogenes and/or misregulation of signal transduction pathways. Chemotherapy and radiotherapy used for the treatment have several side effects. During the recent years, therapeutic strategies involving hormone deprivation (estrogen, androgen), hormone replacements (estrogen analogs), hormone receptor modulators (SERMs), growth factors and cytokines, small-molecule inhibitors, and gene therapy have emerged as a promising alternative to chemo- and radiotherapy. In the present chapter, we have provided an extensive account of tumors associated with the bone and various therapeutic options related to hormone deprivation, hormone replacements, hormone receptor modulators, and hormone inhibition

Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction

Trauma, congenital abnormalities and pathologies such as cancer can cause significant defects in craniofacial bone. Regeneration of the bone in the craniofacial area presents a unique set of challenges due to its complexity and association with various other tissues. Bone grafts and bone cement are the traditional treatment options but pose their own issues with regards to integration and morbidity. This has driven the search for materials which mimic the natural bone and can act as scaffolds to guide bone growth. Novel technology and computer aided manufacturing have allowed us to control material parameters such as mechanical strength and pore geometry. In this chapter, we elaborate the current status of materials and techniques used in fabrication of scaffolds for craniomaxillofacial bone tissue engineering and discuss the future prospects for advancements

Probiotics and Bone Health: It takes GUTS to Improve Bone Density

Probiotics are a class of symbiotic bacteria whose administration in adequate amount provides health benefits to the host by altering the composition of gut microbiota. The gut microbiota is known to regulate both the host immune system and metabolism, leading to increased bone mass by inhibiting bone resorption. Ovariectomy induced estrogen deficiency which mimics postmenopausal osteoporosis in women leads to enhanced bone inflammation and resorption. Recently it has been reported that different strains of bacteria (e.g. Lactobacillus, Bifidobacteria etc.), have important role in gut-bone regulation in ovariectomized mouse. Thus administration of probiotics can open up new avenues in treatment of various inflammatory bone conditions such as osteoporosis and rheumatoid arthritis by modulating the delicate balance between the gut microbiota and immune system.</p

Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance

Osteoporosis is one of the most important but often neglected bone disease associated with aging and postmenopausal condition leading to bone loss and fragility. Probiotics have been associated with various immunomodulatory properties and have the potential to ameliorate several inflammatory conditions including osteoporosis. Lactobacillus acidophilus (LA) was selected as probiotic of choice in our present study due its common availability and established immunomodulatory properties. In the present study, we report for the first time that administration of LA in ovariectomized (ovx) mice enhances both trabecular and cortical bone microarchitecture along with increasing the mineral density and heterogeneity of bones. This effect of LA administration is due to its immunomodulatory effect on host immune system. LA thus skews the Treg-Th17 cell balance by inhibiting osteoclastogenic Th17 cells and promoting anti-osteoclastogenic Treg cells in ovx mice. LA administration also suppressed expression of osteoclastogenic factors (IL-6, IL-17, TNF-α and RANKL) and increased expression of anti-osteoclastogenic factors (IL-10, IFN-γ). Taken together the present study for the first time clearly demonstrates the therapeutic potential of LA as an osteo-protective agent in enhancing bone health (via tweaking Treg-Th17 cell balance) in postmenopausal osteoporosis. Keywords: Probiotics, Lactobacillus acidophilus, Bone heterogeneity, Treg cell, Th17 cell, Osteoporosi

IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage

IL-3 is an important cytokine that regulates hematopoiesis and functions as a link between the immune and the hematopoietic system. In this study, we investigated the role and mechanism of IL-3 action on human osteoclast formation and bone resorption using PBMCs. PBMCs differentiate into functional osteoclasts in the presence of M-CSF and receptor activator of NF-κB ligand as evaluated by 23c6 expression and bone resorption. We found that IL-3 dose-dependently inhibited formation of 23c6-positive osteoclasts, bone resorption and C-terminal telopeptide of type I collagen, a collagen degradation product. The inhibitory effect of IL-3 on bone resorption was irreversible. To investigate the mechanism of IL-3 action, we analyzed the effect of IL-3 on the receptor activator of NF-kB and c-Fms receptors and c-Fos, PU.1, NFAT cytoplasmic 1, and RelB transcription factors essential for osteoclastogenesis. IL-3 significantly inhibited c-Fms and downregulated both PU.1 and c-Fos at both mRNA and protein level. Furthermore, IL-3-treated cells showed increased expression of dendritic cell markers CD1a and CD80 and decreased expression of monocyte/macrophage marker CD14. Interestingly, IL-3 inhibited formation of human osteoclasts derived from blood monocytes and bone marrow cells of osteoporotic individuals. Thus, IL-3 may have therapeutic potential as an antiosteolytic agent in treatment of osteoporosis

Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into multiple cell lineages. Presently, bone marrow is considered as a prime source of MSCs; however, there are some drawbacks and limitations in use of these MSCs for cell therapy. In this study, we demonstrate that human gingival tissue-derived MSCs have several advantages over bone marrow-derived MSCs. Gingival MSCs are easy to isolate, homogenous and proliferate faster than bone marrow MSCs without any growth factor. Importantly, gingival MSCs display stable morphology and do not loose MSC characteristic at higher passages. In addition, gingival MSCs maintain normal karyotype and telomerase activity in long-term cultures, and are not tumorigenic. Thus, we reveal that human gingiva is a better source of MSCs than bone marrow, and large number of functionally competent clinical grade MSCs can be generated in short duration for cell therapy in regenerative medicine and tissue engineering

IL-3 attenuates collagen-induced arthritis by modulating the development of Foxp3<SUP>+</SUP> regulatory T cells

IL-3, a cytokine secreted by Th cells, functions as a link between the immune and the hematopoietic system. We previously demonstrated the potent inhibitory role of IL-3 on osteoclastogenesis, pathological bone resorption, and inflammatory arthritis. In this study, we investigated the novel role of IL-3 in development of regulatory T (Treg) cells. We found that IL-3 in a dose-dependent manner increases the percentage of Foxp3+ Treg cells indirectly through secretion of IL-2 by non-Treg cells. These IL-3-expanded Treg cells are competent in suppressing effector T cell proliferation. Interestingly, IL-3 treatment significantly reduces the severity of arthritis and restores the loss of Foxp3+ Treg cells in thymus, lymph nodes, and spleen in collagen-induced arthritis mice. Most significantly, we show that IL-3 decreases the production of proinflammatory cytokines IL-6, IL-17A, TNF-α , and IL-1 and increases the production of anti-inflammatory cytokines IFN-α and IL-10 in collagen-induced arthritis mice. Thus, to our knowledge, we provide the first evidence that IL-3 play an important role in modulation of Treg cell development in both in vitro and in vivo conditions, and we suggest its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases