Calcium and phosphate supplementation promotes bone cell mineralization: Implications for hydroxyapatite (HA)-enhanced bone formation

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

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The effect of tai chi chuan on bone remodeling and cytokines among breast cancer survivors: A feasibility trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9610 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9610-9610

Author(s):

L. J. Peppone ◽

K. Mustian ◽

R. N. Rosier ◽

K. M. Piazza ◽

D. G. Hicks ◽

...

Keyword(s):

Breast Cancer ◽

Bone Resorption ◽

Bone Formation ◽

Bone Remodeling ◽

Bone Health ◽

Tai Chi ◽

Cell Function ◽

Bone Cell ◽

Post Intervention ◽

Tai Chi Chuan

9610 Background: Weight-bearing exercise may slow the rate of bone loss associated with breast cancer treatment. The purpose of this study is to determine the effect of tai chi chuan (TCC) on bone health, as measured by the changes in the levels of bone resorption and bone formation. This study also aimed to investigate whether changes in bone health were correlated with growth and inflammation markers that serve as regulators of bone cell function. Methods: Female patients (N=16) who completed treatment for breast cancer within the past 30 months were randomly assigned to either the TCC group or the psycho-educational support group without exercise (ST) for 60 minutes, three times a week for a period of 12 weeks. Serum levels of bone resorption (N-telopeptides of type I collagen; NTx) and bone formation (bone specific alkaline phosphatase; BAP) were determined by ELISA at baseline and post-intervention. Using validated methods, a bone remodeling index (BRI) was calculated from levels of NTx and BAP. In addition, pre- and post-intervention levels of insulin-like growth factor binding protein 1 (IGFBP-1) and interleukin-2 (IL-2), markers associated with excessive bone resorption, were measured. Lastly, levels of interleukin-6 (IL-6), believed to enhance bone formation, were measured at both pre- and post-intervention. Results: ANCOVA analyses demonstrated that survivors in the TCC group experienced a greater increase in bone remodeling than those in the ST group (Δ BRITCC=1.6 vs Δ BRIST=0.2; p=0.04). All correlations were determined by Pearson's correlation coefficients. IGFBP-1 was negatively correlated with increasing bone remodeling levels (r=-0.43, p=0.14). IL-2 was also negatively correlated with increasing bone remodeling levels (r=-0.35, p=0.24). IL-6 was positively correlated with increasing bone remodeling levels (r=0.69, p=0.01). Conclusions: This pilot study suggests that TCC has positive effects on bone remodeling through changes in growth and inflammation factors that regulate bone cell function. A larger, more definitive trial examining the influence of TCC on bone remodeling is warranted. Funding: Sally Schindel Cone and R25 CA102618 No significant financial relationships to disclose.

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Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production

Acta Endocrinologica ◽

10.1530/acta.0.1260329 ◽

1992 ◽

Vol 126 (4) ◽

pp. 329-337 ◽

Cited By ~ 63

Author(s):

Florence A Tremollieres ◽

Donna D Strong ◽

David J Baylink ◽

Subburaman Mohan

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Bone Formation ◽

Conditioned Medium ◽

Bone Cell ◽

Human Bone ◽

Osteoblastic Cells ◽

Human Bone Cell ◽

Bone Cell Proliferation ◽

Human Osteoblastic Cells

Recent clinical studies suggest that progesterone may be involved in the regulation of bone turnover and could promote bone formation. This study was undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG derivative) may have a direct effect on human bone cells and, if so, whether growth factor production could be involved in promoting this effect. The osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells derived from iliac crest were used as in vitro model systems. Progesterone and promegestone were found to significantly increase [3H]thymidine incorporation in TE8 5 cells in a dose-dependent manner at concentrations ranging from 10−12to 10−8 mol/l after four days of cultivation (p<0.01, ANOVA). Consistent with this response in the TE85 cells, progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment (p<0.05. ANOVA). To determine whether this effect on cell proliferation was mediated by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1, IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of both TE85 and human osteoblast cells. While no significant changes in IGF-1 levels were found in the conditioned media of progesterone and promegestone treated cultures, progesterone and promegestone at the concentration of 5 nmol/l significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in the conditioned medium of TE8 5 cells as compared to control. Similarly, a 4.1 and 1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and promegestone in human osteoblastic cells. Consistent with the increased secretion of IGF-2 into the conditioned medium, IGF-2 mRNA levels were found to be increased in TE85 cells. A 4.9 kb transcript was increased 2.7 and 3.7-fold respectively after 6 h of exposure to 5 nmol/l of progesterone and promegestone as compared to control. Western ligand blot analysis of conditioned medium collected from TE85 and human osteoblast cell cultures treated with progesterone and promegestone revealed no changes in the levels of IGFBP-3 and IGFBP-4 after 48 h of treatment. Consistent with these results, the IGFBP-4 mRNA level was unaffected. These data suggest that both progesterone and promegestone stimulate human bone cell proliferation and that the mechanism may in part involve increased IGF-2 secretion. Because IGF-2 has been proposed to play a potential role in the coupling of bone formation to bone resorption, it follows that progesterone deficiency may be involved in the uncoupling that occurs in postmenopause. In any case, the findings that progesterone and promegestone have direct effects on bone formation could have physiological implications.

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The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro

Bone ◽

10.1016/8756-3282(96)00080-4 ◽

1996 ◽

Vol 18 (6) ◽

pp. 517-523 ◽

Cited By ~ 366

Author(s):

E Canalis

Keyword(s):

Bone Formation ◽

Bone Cell ◽

Cell Replication ◽

Strontium Salt

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Lactoferrin Is a Potent Regulator of Bone Cell Activity and Increases Bone Formation in Vivo

Endocrinology ◽

10.1210/en.2003-1307 ◽

2004 ◽

Vol 145 (9) ◽

pp. 4366-4374 ◽

Cited By ~ 170

Author(s):

Jillian Cornish ◽

Karen E. Callon ◽

Dorit Naot ◽

Kate P. Palmano ◽

Tatjana Banovic ◽

...

Keyword(s):

Bone Formation ◽

Cell Activity ◽

Bone Cell

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The simultaneous analysis of mesenchymal stem cells and early osteocytes accumulation in osteoarthritic femoral head sclerotic bone

Rheumatology ◽

10.1093/rheumatology/kez130 ◽

2019 ◽

Vol 58 (10) ◽

pp. 1777-1783 ◽

Cited By ~ 8

Author(s):

Dragos C Ilas ◽

Sarah M Churchman ◽

Thomas Baboolal ◽

Peter V Giannoudis ◽

Joseph Aderinto ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Subchondral Bone ◽

Bone Cell ◽

Novel Therapy ◽

Marked Accumulation ◽

Close Juxtaposition ◽

Therapy Development

Abstract Objective OA subchondral bone is a key target for therapy development. Osteocytes, the most abundant bone cell, critically regulate bone formation and resorption. Their progenitors, mesenchymal stem cells (MSCs), display altered behaviour in osteoarthritic subchondral bone. This study investigated the relationships between native osteocytes and native MSCs in osteoarthritic femoral heads. Methods To avoid culture manipulations, a bone treatment procedure was developed to simultaneously obtain pure osteocyte-enriched fragments and matched native CD45-CD271+ MSCs. Gene expression in osteocytes and MSCs was compared between healthy and OA bone and selected molecules were examined by immunohistochemistry in relation to OA tissue pathology. Cell sorting and standard trilineage differentiation assays were employed to test OA MSC functionality. Results Native osteocyte enrichment was confirmed histologically and by higher-level osteocyte maturation transcripts expression, compared with purified MSCs. Compared with healthy bone, native OA osteocytes expressed 9- and 4-fold more early/embedding osteocyte molecules E11 and MMP14, and 6-fold more osteoprotegerin (P<0.01). CD271+ MSCs accumulated in the regions of bone sclerosis (9-fold, P<0.0001) in close juxtaposition to trabeculae densely populated with morphologically immature E11-positive osteocytes (medians of 76% vs 15% in non-sclerotic areas, P<0.0001), and osteoblasts. Gene expression of OA MSCs indicated their bone formation bias, with retained multipotentiality following culture-expansion. Conclusions In human late-stage OA, osteogenically-committed MSCs and adjacent immature osteocytes exhibit a marked accumulation in sclerotic areas. This hitherto unappreciated MSC-early osteocyte axis could be key to understanding bone abnormalities in OA and represents a potential target for novel therapy development in early disease.

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Effects of nano-engineered surfaces on osteoblast adhesion, growth, differentiation, and apoptosis

Proceedings of the Institution of Mechanical Engineers Part N Journal of Nanomaterials Nanoengineering and Nanosystems ◽

10.1177/2397791419886778 ◽

2019 ◽

Vol 234 (1-2) ◽

pp. 59-66

Author(s):

Raheleh Miralami ◽

John G Sharp ◽

Fereydoon Namavar ◽

Curtis W Hartman ◽

Kevin L Garvin ◽

...

Keyword(s):

Cell Adhesion ◽

Bone Formation ◽

Zirconium Oxide ◽

Ion Beam ◽

Bone Cell ◽

Calcium Deposition ◽

Deposition Technique ◽

Ion Beam Assisted Deposition ◽

Osteoblast Adhesion ◽

Glass Surfaces

Modifying implant surfaces to improve their biocompatibility by enhancing osteoblast activation, growth, differentiation, and induction of greater bone formation with stronger attachments should result in improved outcomes for total joint replacement surgeries. This study tested the hypothesis that nano-structured surfaces, produced by the ion beam-assisted deposition method, enhance osteoblast adhesion, growth, differentiation, bone formation, and maturation. The ion beam-assisted deposition technique was employed to deposit zirconium oxide films on glass substrates. The effects of the ion beam-assisted deposition technique on cellular functions were investigated by comparing adhesion, proliferation, differentiation, and apoptosis of the human osteosarcoma cell line SAOS-2 on coated versus uncoated surfaces. Ion beam-assisted deposition nano-coatings enhanced initial cell adhesion assessed by the number of 4′,6-diamidino-2-phenylindole–stained nuclei on zirconium oxide nano-coated surfaces compared to glass surfaces. This nano-modification also increased cell proliferation as measured by mitochondrial dehydrogenase activity. Moreover, the ion beam-assisted deposition technique improved cell differentiation as determined by the formation of mineralized bone nodules and by the rate of calcium deposition, both of which are in vitro indicators of the successful bone formation. However, programmed cell death assessed by Annexin V staining and flow cytometry was not statistically significantly different between nano-surfaces and glass surfaces. Overall, the results indicate that nano-crystalline zirconium oxide surfaces produced by the ion beam-assisted deposition technique are superior to uncoated surfaces in supporting bone cell adhesion, proliferation, and differentiation. Thus, surface properties altered by the ion beam-assisted deposition technique enhanced bone formation and may increase the biocompatibility of bone cell–associated surfaces.

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