ROLE OF OSTEOCLASTS IN THE BIOCORROSION OF METAL IMPLANTS

poster abstractMini implants (MIs), typically composed of stainless steel (SS) or titanium alloy (Ti), have recently emerged as superior alternatives to traditional dental and orthopedic implants. When a metal implant is inserted into bone, a process called bone remodeling is triggered near the implant. Bone remodeling involves the activity of osteoblasts (OBs), which produce new bone tissue, and osteoclasts (OCs), which degrade and digest bone. OCs degrade bone by acidifying the extracellular environment and secreting hydrolytic enzymes that degrade the extracellular matrix. However, the acidification of the extracellular environment can potentially lead to the biological corrosion of metal implants after implantation. This may have important consequences such as cell toxicity, decreased osseointegration of the implant, and implant loosening. The objective of this study is to determine if implants made from Ti are more resistant to OC-mediated biocorrosion than stainless steel (SS) implants. We hypothesize that biocorrosive activity by OCs will be greater on SS than titanium. To assess the biocorrosive effects of OCs on SS and Ti, the top face of 150 µm thick sections of each metal were scanned using a Proscan 2000 Scantron to provide accurate three dimensional surface measurements of the metals before introduction of OCs. OC precursors were isolated from the bone marrow of C57/bl6 mice and differentiated with macrophage colony stimulating factor and receptor activator of NF-kappaB ligand for 7 days in the presence of either SS or Ti metals. The metals discs were then removed and rescanned with the Proscan Scantron and changes in the surface measurements before and after OC growth was calculated. OCs were fixed and stained for tartrate-resistant acid phosphatase, a marker of mature OCs, and counted. Our preliminary findings revealed that the surface roughness of SS was reduced to a greater extent than Ti metals. OC number was also reduced in cultures containing SS compared with Ti. These findings suggest SS may be more susceptible to OC-mediated biocorrosion than Ti-based metal implants. Although the physiological implications are unclear, we speculate that sustained corrosion of SS can negatively affect the long-term stability of implants in vivo

Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration Via Distinct and Overlapping Mechanisms

Osteoblast differentiation and migration are necessary for bone formation during bone remodeling. Mice lacking the proline-rich tyrosine kinase Pyk2 (Pyk2-KO) have increased bone mass, in part due to increased osteoblast proliferation. Megakaryocytes (MKs), the platelet-producing cells, also promote osteoblast proliferation in vitro and bone-formation in vivo via a pathway that involves Pyk2. In the current study, we examined the mechanism of action of Pyk2, and the role of MKs, on osteoblast differentiation and migration. We found that Pyk2-KO osteoblasts express elevated alkaline phosphatase (ALP), type I collagen and osteocalcin mRNA levels as well as increased ALP activity, and mineralization, confirming that Pyk2 negatively regulates osteoblast function. Since Pyk2 Y402 phosphorylation is important for its catalytic activity and for its protein-scaffolding functions, we expressed the phosphorylation-mutant (Pyk2(Y402F) ) and kinase-mutant (Pyk2(K457A) ) in Pyk2-KO osteoblasts. Both Pyk2(Y402F) and Pyk2(K457A) reduced ALP activity, whereas only kinase-inactive Pyk2(K457A) inhibited Pyk2-KO osteoblast migration. Consistent with a role for Pyk2 on ALP activity, co-culture of MKs with osteoblasts led to a decrease in the level of phosphorylated Pyk2 (pY402) as well as a decrease in ALP activity. Although, Pyk2-KO osteoblasts exhibited increased migration compared to wild-type osteoblasts, Pyk2 expression was not required necessary for the ability of MKs to stimulate osteoblast migration. Together, these data suggest that osteoblast differentiation and migration are inversely regulated by MKs via distinct Pyk2-dependent and independent signaling pathways. Novel drugs that distinguish between the kinase-dependent or protein-scaffolding functions of Pyk2 may provide therapeutic specificity for the control of bone-related diseases

ROLE OF OSTEOCLASTS IN THE BIOCORROSION OF METAL IMPLANTS

poster abstractMini implants (MIs), typically composed of stainless steel (SS) or titanium alloy (Ti), have recently emerged as superior alternatives to traditional dental and orthopedic implants. When a metal implant is inserted into bone, a process called bone remodeling is triggered near the implant. Bone remodeling involves the activity of osteoblasts (OBs), which produce new bone tissue, and osteoclasts (OCs), which degrade and digest bone. OCs degrade bone by acidifying the extracellular environment and secreting hydrolytic enzymes that degrade the extracellular matrix. However, the acidification of the extracellular environment can potentially lead to the biological corrosion of metal implants after implantation. This may have important consequences such as cell toxicity, decreased osseointegration of the implant, and implant loosening. The objective of this study is to determine if implants made from Ti are more resistant to OC-mediated biocorrosion than stainless steel (SS) implants. We hypothesize that biocorrosive activity by OCs will be greater on SS than titanium. To assess the biocorrosive effects of OCs on SS and Ti, the top face of 150 µm thick sections of each metal were scanned using a Proscan 2000 Scantron to provide accurate three dimensional surface measurements of the metals before introduction of OCs. OC precursors were isolated from the bone marrow of C57/bl6 mice and differentiated with macrophage colony stimulating factor and receptor activator of NF-kappaB ligand for 7 days in the presence of either SS or Ti metals. The metals discs were then removed and rescanned with the Proscan Scantron and changes in the surface measurements before and after OC growth was calculated. OCs were fixed and stained for tartrate-resistant acid phosphatase, a marker of mature OCs, and counted. Our preliminary findings revealed that the surface roughness of SS was reduced to a greater extent than Ti metals. OC number was also reduced in cultures containing SS compared with Ti. These findings suggest SS may be more susceptible to OC-mediated biocorrosion than Ti-based metal implants. Although the physiological implications are unclear, we speculate that sustained corrosion of SS can negatively affect the long-term stability of implants in vivo

ROLE OF OSTEOCLASTS IN THE BIOCORROSION OF METAL IMPLANTS

poster abstractMini implants (MIs), typically composed of stainless steel (SS) or titanium alloy (Ti), have recently emerged as superior alternatives to traditional dental and orthopedic implants. When a metal implant is inserted into bone, a process called bone remodeling is triggered near the implant. Bone remodeling involves the activity of osteoblasts (OBs), which produce new bone tissue, and osteoclasts (OCs), which degrade and digest bone. OCs degrade bone by acidifying the extracellular environment and secreting hydrolytic enzymes that degrade the extracellular matrix. However, the acidification of the extracellular environment can potentially lead to the biological corrosion of metal implants after implantation. This may have important consequences such as cell toxicity, decreased osseointegration of the implant, and implant loosening. The objective of this study is to determine if implants made from Ti are more resistant to OC-mediated biocorrosion than stainless steel (SS) implants. We hypothesize that biocorrosive activity by OCs will be greater on SS than titanium. To assess the biocorrosive effects of OCs on SS and Ti, the top face of 150 µm thick sections of each metal were scanned using a Proscan 2000 Scantron to provide accurate three dimensional surface measurements of the metals before introduction of OCs. OC precursors were isolated from the bone marrow of C57/bl6 mice and differentiated with macrophage colony stimulating factor and receptor activator of NF-kappaB ligand for 7 days in the presence of either SS or Ti metals. The metals discs were then removed and rescanned with the Proscan Scantron and changes in the surface measurements before and after OC growth was calculated. OCs were fixed and stained for tartrate-resistant acid phosphatase, a marker of mature OCs, and counted. Our preliminary findings revealed that the surface roughness of SS was reduced to a greater extent than Ti metals. OC number was also reduced in cultures containing SS compared with Ti. These findings suggest SS may be more susceptible to OC-mediated biocorrosion than Ti-based metal implants. Although the physiological implications are unclear, we speculate that sustained corrosion of SS can negatively affect the long-term stability of implants in vivo

Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice.

Background: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. Methods: Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. Results and conclusion: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D2 and 25(OH)D3 is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing