NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis.

In this study we investigated the effect of NF-kB signaling blockade on polymethylmethacrylate (PMMA) particle-induced osteoclastogenesis in vitro. We first established effective blockade of NF-kB activity as tested by electrophoretic mobility shift assays (EMSA). Particle-induced NF-kB activation in murine osteoclast precursor cells (CSF-1-dependent bone marrow macrophages) was markedly reduced by co-treatment of the cells with the NF-kB inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and Calpain Inhibitor I (CPI).

Direct inhibition of NF-kappa B blocks bone erosion associated with inflammatory arthritis.

Inflammatory arthritis is associated with devastating joint tissue destruction and periarticular bone erosion. Although secreted products of infiltrating immune cells perpetuate the inflammatory response, the osteolytic component of this disease is a direct result of localized recruitment and activation of osteoclasts. Given that NF-kappaB plays a central role in both processes, the function of this transcription factor was examined.

Bone loss following tendon laceration, repair and passive mobilization.

Little is known about the localized changes in bone mass that occur following tendon or ligament injury. Interruption of normal load transfer at the insertion site will presumably lead to a localized loss of bone, although few data exist to support this claim. To test this hypothesis, we transected the canine flexor digitorum profundus (FDP) tendon from its insertion, and either repaired it using a trans-osseous suture technique or left it unrepaired (laceration only).

Shoulder disorders in the skeletally immature throwing athlete.

Shoulder injuries are common in young throwing athletes. Most injuries are overuse types related to excessive pitch counts, premature use of breaking pitches, and improper pitching mechanics. These etiologic factors should be recognized early and treated.

The rediscovery and isolation of TFPI.

Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type proteinase inhibitor that produces factor (F)Xa-dependent feedback inhibition of the factor VIIa/tissue factor (FVIIa/TF) catalytic complex that is responsible for the initiation of coagulation. Since 1985, when Rapaport and colleagues reported that the lipoprotein fraction of plasma contained a FXa-dependent inhibitor of FVIIa/TF, myriad articles have established its biochemical structure, its mechanism of action, and its physiological importance. This brief personal account reviews historical studies that established the existence of the inhibitor and the events that led to its initial isolation.

Ulnar and median nerve palsy in long-distance cyclists. A prospective study.

Background: Although case reports have identified the presence of distal ulnar nerve sensory and motor dysfunction in long-distance cyclists, the actual incidence of this condition, referred to as "cyclist's palsy," is unknown.

Purpose: To determine the incidence of distal ulnar nerve compression in cyclists.

Study Design: Prospective study.

Glycosyl phosphatidylinositol anchorage of tissue factor pathway inhibitor.

Background: The endothelium is a major source of tissue factor pathway inhibitor (TFPI), the endogenous regulator of TF-induced coagulation, and a significant proportion of the expressed TFPI remains associated with the endothelial surface.

Methods And Results: Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment reduced TFPI at the surface of cultured endothelial cells by approximately 80%, and at least a portion of the TFPI released by PI-PLC contained an intrinsic glycosylphosphatidylinositol (GPI) anchor that is recognized by anti-crossreactive determinant antibodies. Endothelial cells express both of the alternatively spliced forms of TFPI mRNA at a ratio of TFPIbeta/TFPIalpha mRNA of approximately 0.

Two-portal repair of canine flexor tendon insertion site injuries: histologic and immunohistochemical characterization of healing during the early postoperative period.

Purpose: In vivo animal studies have indicated that the complex structure of the tendon-bone interface may not be restored after repair even under optimal conditions. Controversy exists about the histologic findings in the early postoperative period after tendon reattachment to bone; this may have impact on biomechanical properties. The objective was to study the histologic structure and immunohistochemical staining of the tendon-bone interface in a large model of digital flexor tendon-bone repair.

Time-dependent inhibitory effects of indomethacin on spinal fusion.

Background: The use of nonsteroidal anti-inflammatory drugs following spine arthrodesis is discouraged because of the negative effects on bone-healing. We are not aware of any data regarding when nonsteroidal anti-inflammatory drugs may be safely resumed postoperatively. We hypothesized that these drugs have a time-dependent deleterious effect on fusion, with the greatest inhibition during the early phases of fusion.

Neovascularization of the flexor digitorum profundus tendon after avulsion injury: an in vivo canine study.

Purpose: The changes in matrix material properties and intrinsic vascularization that have been noted in intrasynovial tendon stumps after avulsion injury may be of considerable clinical relevance with regard to the results of surgical repair. Our objective was to determine both the time course and the source of neovascularization of the tendon stump in an in vivo canine model of flexor digitorum profundus (FDP) avulsion after a clinically relevant delay in diagnosis.

Method: The FDP tendon was released from bone directly by sharp dissection and the vinculum brevis profundus was lacerated, simulating an avulsion injury with interruption of the vascular supply to the tendon stump.

The Lichtman classification for Kienböck's disease: an assessment of reliability.

Purpose: The correct identification of Lichtman stage 3A and 3B Kienböck's disease is crucial for treatment purposes. The present study evaluates the reliability of the Lichtman classification, with specific attention to differentiating stage 3A and 3B.

Methods: Four reviewers evaluated wrist radiographs from 39 patients with Kienböck's disease.

Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats.

Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor cells for mesenchymal tissues. These cells may also provide a potential therapy for bone repair. Our previous studies showed that MSC engineered with the gene for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were capable of differentiating into osteoblast lineage and inducing autologous bone formation in several animal models.

Arthroscopic treatment of post-traumatic elbow contracture.

The purpose of this study was to evaluate range of motion and patient-reported outcome after complete arthroscopic release of post-traumatic elbow contracture. Fourteen consecutive patients who underwent elbow arthroscopy and capsular release were reviewed retrospectively at a minimum follow-up of 1 year. Pain and range of motion were measured.

Analysis of long-term cemented total hip arthroplasty retrievals.

A detailed biomechanical, histologic, and histomorphometric analysis of autopsy specimens from patients who previously had cemented total hip arthroplasty has helped to elucidate the skeletal response to cemented components. Bone cement has the capacity to provide long-term implant stability. The biologic response to polyethylene wear debris has a more critical effect on destabilization of cemented sockets compared with the femoral side.

The effect of cyclooxygenase-2 inhibitors on spinal fusion.

Background: Spine surgeons discourage the use of nonsteroidal anti-inflammatory drugs following spine arthrodesis because of their inhibitory effect on bone-healing. To our knowledge, there are no data on the effects of the new cyclooxygenase-2 inhibitors on bone-healing. We undertook this study to determine the effects of these more selective nonsteroidal anti-inflammatory drugs on spinal fusion in a rabbit model.

Sirolimus-induced leukocytoclastic vasculitis.

A 41-year-old white woman with cystic fibrosis underwent lung transplantion that was complicated by cyclosporine-induced nephrotoxicity, which required kidney transplantation. Three years after the renal transplant, sirolimus was substituted for mycophenolate mofetil in a maintenance immunosuppressive regimen that consisted of cyclosporine and prednisone, with the hope of lowering cyclosporine concentrations and avoiding the nephrotoxic effects. Three weeks after the initiation of sirolimus, the patient developed palpable purpura on the bilateral lower extremities that resolved after discontinuation of sirolimus and reappeared with rechallenge.

The role of Sp1 in BMP2-up-regulated Erk2 gene expression.

Extracellular signal-regulated kinase (Erk) is an important component in many cellular processes, including cell differentiation and proliferation. We previously showed that Erk is involved in BMP2-induced osteoblastic differentiation in mesenchymal progenitor cells and Erk protein level is up-regulated under BMP2 inducement. In this study, the molecular mechanism which mediates the regulation of Erk2 gene expression by BMP2 was investigated.

Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced whole-bone strength and resistance to fracture.

The senescence accelerated mouse strain P6 (SAMP6) has emerged as a useful model of senile osteoporosis because it has many features of the disease, including low trabecular bone formation and low areal bone density. We further characterized the SAMP6 model of senile osteoporosis by comparing morphological, mechanical, and densitometric properties of femurs and tibias from SAMP6 mice to those of the control strain (SAMR1) at 4 months and 12 months of age. SAMP6 long bones had increased periosteal width and endosteal area (p < 0.

Recent progress in flexor tendon healing.

Although advances in the treatment of flexor tendon injuries have led to improved clinical outcomes during the past several decades, a subset of patients continue to experience a loss of function. Using a canine model of sharp transection of the flexor digitorum profundus tendon followed by repair and rehabilitation using clinically relevant techniques, we have examined the influence of multistrand suture and postoperative rehabilitation variables on digital function and tendon strength. Our findings highlight the critical role of repair technique in providing a stiff and strong repair and indicate that continued refinement of suture techniques is warranted in order to minimize repair-site elongation (gap).

Repair of flexor digitorum profundus tendon avulsions from bone: an ex vivo biomechanical analysis.

Avulsions or distal transections of the flexor digitorum profundus tendon are typically repaired by direct suture of the tendon stump to the distal phalanx. The optimal repair technique to withstand in vivo rehabilitation forces is unknown. Our objective was to determine the time-zero tensile mechanical properties of 4-strand tendon-bone repair site constructs performed with 3-0 and 4-0 sutures and with modified Kessler and modified Becker grasping techniques.

Microfibril-associated glycoprotein-2 interacts with fibrillin-1 and fibrillin-2 suggesting a role for MAGP-2 in elastic fiber assembly.

Elastic fibers are composed of the protein elastin and a network of 10-12 nm microfibrils. The microfibrillar proteins include, among others, the fibrillins and microfibril-associated glycoproteins-1 and -2 (MAGP-1 and MAGP-2). Little is known about how microfibrillar proteins interact to support fiber assembly.

Tumor necrosis factor-alpha mediates polymethylmethacrylate particle-induced NF-kappaB activation in osteoclast precursor cells.

Tumor necrosis factor-alpha (TNF) is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of implant particle-induced osteolysis. The nuclear transcription factor NF-kappaB mediates TNF signaling and this transcription complex is necessary for osteoclastogenesis. Because polymethylmethacrylate (PMMA) particles cause osteolysis, we reasoned the PMMA would induce NF-kappaB activation.