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Nancy E Lane

Publications and source records attributed to Nancy E Lane.

27 records · Page 2Linked to original sources
PubMed2003

The signaling adapter protein DAP12 regulates multinucleation during osteoclast development.

UNLABELLED: Deficiency of the signaling adapter protein DAP12 is associated with bony abnormalities in both mice and humans. We identify specific DAP12-associated receptors expressed by osteoclasts and examine function of DAP12 in murine osteoclasts in vivo and in vitro. These data show a new role for DAP12 signaling in regulating formation of multinucleated osteoclasts. INTRODUCTION: Osteoclasts are bone-resorbing cells derived from hematopoietic precursors in the myeloid lineage. In other myeloid cell types, the signaling adapter protein DAP12 transmits activating signals on ligation of a DAP12-associated receptor (DAR). The aim of this study was to clarify the role of DAP12 signaling during osteoclast development. MATERIALS AND METHODS: Osteoclasts from DAP12 -/- or control mice were analyzed in vitro for morphology, function, and for osteoclast markers. DARs were identified in osteoclast cultures through reverse transcriptase-polymerase chain reaction (RT-PCR). Bone density of DAP12 -/- and control mice were analyzed by microcomputed tomography. DAP12 -/- osteoclasts were retrovirally reconstituted with DAP12. RAW264.7 cells were transfected with FLAG-tagged DAP12 or TREM2 and stimulated by anti-FLAG antibody during in vitro osteoclastogenesis. RESULTS: C57BL/6 DAP12-deficient mice have higher bone mass than C57BL/6 wildtype controls. We verified the presence of DAP12 in pre-osteoclasts and osteoclasts derived from C57BL/6 or the pre-osteoclast line RAW 264.7 and identified the DARs expressed. DAP12 -/- osteoclasts developed in vitro with macrophage colony-stimulating factor (M-CSF) and RANKL formed only intensely TRACP+ mononuclear cells and failed to generate multinuclear osteoclasts. These mononuclear cells are functional osteoclast-like cells because, by RT-PCR, they express other osteoclast markers and generate resorption pits on dentine slices, although quantitative assessment of bone resorption shows decreased resorption by DAP12 -/- osteoclasts compared with C57BL/6 osteoclasts. Restoration of DAP12 expression by retroviral transduction of DAP12 -/- osteoclast precursors rescued in vitro osteoclast multinucleation. Direct stimulation of DAP12 expressed in RAW264.7 during in vitro osteoclastogenesis led to a marked increase in the number of TRACP+ multinucleated osteoclast-like cells formed. CONCLUSION: Our studies indicate that stimulation of the DAP12 adapter protein plays a significant role in formation of multinuclear osteoclasts and that DAP12 and DARs likely participate in the regulation of bony remodeling.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Association of nitrate use with risk of new radiographic features of hip osteoarthritis in elderly white women: the study of osteoporotic fractures.

OBJECTIVE: To examine the association between nitrate medication use and the development of new radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Pelvic radiographs were obtained at baseline and a mean of 8.3 years later in 5,987 women, age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. Atlas-standardized individual radiographic features (IRFs) of OA were assessed and minimal joint space was measured on paired films. New radiographic findings of hip OA were defined as the development in hips free of these findings at baseline: 1) joint space narrowing (JSN), which consisted of either a MJS < or =1.5 mm or an IRF score indicating lateral JSN > or =2 or medial JSN > or =3; 2) an IRF score for osteophytes of > or =2 in any location; or 3) a summary grade of 2 or more (at least 2 IRFs present). Nitrate use was recorded by interview at years 6 and 8. Logistic and linear regression analyses were performed to determine the association of nitrate use with new radiographic findings of hip OA, adjusting for age, weight, height, bone mineral density, and estrogen. RESULTS: Compared with no reported use of nitrates, we found significant associations between use of nitrates at 1 clinic visit and new JSN (odds ratio [OR] 1.94, 95% confidence interval [95% CI] 1.18-3.17, P = 0.009), new osteophyte formation (OR 1.70, 95% CI 1.03-2.88, P = 0.04), and any new radiographic finding of hip OA or total hip arthroplasty for OA (OR 1.71, 95% CI 1.16-2.52, P = 0.007). Any nitrate use was associated with an increased risk of developing summary grade 3 or greater hip OA (OR 1.84, 95% CI 1.03-3.31, P = 0.041), but not with any other incident findings of OA. CONCLUSION: Older women using nitrates may have an increased risk of developing new radiographic findings of hip OA.

Aged↗
PubMed2003

A review of anabolic therapies for osteoporosis.

Osteoporosis results from a loss of bone mass and bone structure such that the bone becomes weak and fractures with very little trauma. Until recently, the approved osteoporosis therapies prevented more bone loss by altering osteoclast activity and lifespan. Recently, attention has turned away from osteoclast inhibition to agents that can stimulate the osteoblast to form new bone, or anabolic agents. This article reviews both approved and experimental anabolic agents that improve bone mass by improving osteoblast activity, or increasing osteoblast number. The use of the anabolic agents to improve bone mass and strength followed by agents that prevent the new bone mass from being lost may offer the ability to cure osteoporosis and reduce bone fracture healing time.

Anabolic Agents↗
PubMed2003

Effect of glucocorticoids on bone density.

Glucocorticoid therapy is the most common cause of secondary iatrogenic osteoporosis. The bone loss occurs predominantly due to a decrease in bone formation, although increased bone resorption also occurs. Glucocorticoids induce osteoblast apoptosis and increase osteoclast survival and activity. Most of these effects are mediated through the RANKL-OPG system but perturbations in gonadal hormone activity and calcium balance may also contribute significantly to bone loss. Future therapies in the treatment and prevention of glucocorticoid-induced osteoporosis may be targeted at restoring the hormonal and cytokine balance to nullify the apoptotic effect of glucocorticoids on bone forming cells.

Bone Density↗
PubMed2003

Both hPTH(1-34) and bFGF increase trabecular bone mass in osteopenic rats but they have different effects on trabecular bone architecture.

UNLABELLED: Osteoporosis is a syndrome of excessive skeletal fragility that results from both the loss of trabecular bone mass and trabecular bone connectivity. Recently, bFGF has been found to increase trabecular bone mass in osteoporotic rats. The purpose of this study was to compare how trabecular bone architecture, bone cell activity, and strength are altered by two different bone anabolic agents, bFGF and hPTH(1-34), in an osteopenic rat model. MATERIALS AND METHODS: Six-month-old female Sprague-Dawley rats (n = 74) were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 2 months. Then OVX rats were subcutaneously injected with basic fibroblast factor (bFGF; 1 mg/kg, 5 days/week), human parathyroid hormone [hPTH(1-34); 40 microg/kg, 5 days/week], or vehicle for 60 days (days 60-120). Sham-operated and one group of OVX animals were injected with vehicle. Biochemical markers of bone turnover (urinary deoxypyridinoline cross-links; Quidel Corp., San Diego, CA, USA) and serum osteocalcin (Biomedical Technologies, Stroughton, MA, USA) were obtained at study days 0, 60, 90, and 120 and analyzed by ELISA. At death, the right proximal tibial metaphysis was removed, and microcomputed tomography was performed for trabecular bone structure and processed for histomorphometry to assess bone cell activity. The left proximal tibia was used for nanoindentation/mechanical testing of individual trabeculae. The data were analyzed with Kruskal Wallis and post hoc testing as needed. RESULTS: Ovariectomy at day 60 resulted in about a 50% loss of trabecular bone volume compared with sham-treated animals. By day 120 post-OVX, OVX + vehicle treated animals had decreased trabecular bone volume, connectivity, number, and high bone turnover compared with sham-operated animals [p < 0.05 from sham-, hPTH(1-34)-, and bFGF-treated groups]. Treatment of OVX animals with bFGF and hPTH(1-34) both increased trabecular bone mass, but hPTH(1-34) increased trabecular thickness and bFGF increased trabecular number and connectivity. Histomorphometry revealed increased mineralizing surface and bone formation rate in both bFGF and hPTH(1-34) animals. However, osteoid volume was greater in bFGF-treated animals compared with both the hPTH(1-34) and OVX + vehicle animals (p < 0.05). Nanoindentation by atomic force microscope was performed on approximately 20 individual trabeculae per animal (three animals per group) and demonstrated that elastic modulus and hardness of the trabeculae in bFGF-treated animals were similar to that of the hPTH-treated and sham + vehicle-treated animals. CONCLUSION: Both hPTH(1-34) and bFGF are anabolic agents in the osteopenic female rat. However, hPTH(1-34) increases trabecular bone volume primarily by thickening existing trabeculae, whereas bFGF adds trabecular bone mass through increasing trabecular number and trabecular connectivity. These results suggest the possibility of sequential treatment paradigms for severe osteoporosis.

Anabolic Agents↗
PubMed2002

Very low prevalence of hip osteoarthritis among Chinese elderly in Beijing, China, compared with whites in the United States: the Beijing osteoarthritis study.

OBJECTIVE: To compare the prevalence of osteoarthritis (OA) of the hip among elderly persons in China and the US. METHODS: We recruited a population-based sample of 1,506 persons (82% of those enumerated) ages > or = 60 years living in Beijing, China. Subjects answered questions about joint symptoms and underwent radiography of the pelvis. Radiographs of the Beijing subjects were intermingled with hip radiographs of white women ages > or = 65 years from the Study of Osteoporotic Fractures (SOF) and white men and women ages 60-74 years from the First National Health and Nutrition Examination Survey (NHANES-I) and were then interpreted. Radiographic hip OA was defined as the presence of 1 of the following 3 findings in either hip: minimum joint space of < or = 1.5 mm, definite osteophytes and joint space narrowing, or > or = 3 radiographic features of OA. Symptomatic hip OA was defined as both radiographic OA and hip pain. RESULTS: The crude prevalence of radiographic hip OA in Chinese ages 60-89 years was 0.9% in women and 1.1% in men; it did not increase with age. Chinese women had a lower age-standardized prevalence of radiographic hip OA compared with white women in the SOF (age-standardized prevalence ratio 0.07) and the NHANES-I (prevalence ratio 0.22). Chinese men had a lower prevalence of radiographic hip OA compared with white men of the same age in the NHANES-I (prevalence ratio 0.19). There were no cases of symptomatic hip OA in the Chinese men and only 1 case in the Chinese women; 35 cases were expected in both sexes. CONCLUSION: This is the first population-based study of hip OA in China to use standardized radiographic methods and definitions. We found that hip OA was 80-90% less frequent than in white persons in the US. Identification of the genetic and environmental factors that underlie these differences may help elucidate the etiology and prevention of hip OA.

Aged↗
PubMed2002

The longterm outcome of osteoarthritis: rates and predictors of joint space narrowing in symptomatic patients with knee osteoarthritis.

OBJECTIVE: To determine the rate of progression of radiographic joint space narrowing (JSN) and the factors that predict it in symptomatic clinic patients with knee osteoarthritis (OA). METHODS: In total 1,507 patients with knee OA were studied with extended weight-bearing anterior-posterior views of the knee as part of a longitudinal study of longterm outcomes of osteoarthritis (OA). Baseline demographic and severity measurements included body mass index (BMI), pain, global severity, Health Assessment Questionnaire disability, and erythrocyte sedimentation rate. Rates and predictors of progression were obtained by Kaplan-Meier survival analyses and Cox regressions using a JSN score of 3 as "failure." RESULTS: For the 1,232 patients who had not reached the endpoint narrowing score of 3 when first evaluated, the 75th and 50th survival times (time to JSN = 3) were 11.27 and 17.84 years for those with JSN = 0 at onset, 7.41 and 12.03 years for those with JSN = 1 at onset, and 4.49 and 7.44 years for those with JSN = 2 at onset. The corresponding yearly incidence rates for the 3 initial groups were 0.017, 0.032, and 0.077. In multivariate Cox models, initial JSN, BMI, symptom duration, and global severity were predictors of progression, but only JSN was a strong predictor. BMI predicted JSN in those with JSN = 0 at onset, but not in patients with more severe disease. Although contralateral JSN predicted progression, it was only of value with initial homolateral JSN scores of 0. Assessment of homolateral osteophytes aided prediction in patients with initial JSN = 0, but was of much less help when JSN had a higher severity score. CONCLUSION: The risk of progression in clinical OA patients with radiographic abnormalities is substantial. Nonradiographic predictors of OA progression (e.g., BMI) are weak predictors of radiographic progression compared to current radiographic status. Rates of progression are greatest in those with established radiographic abnormalities. Osteophytes are of limited additional values once JSN = 2 is present. Contralateral radiographic abnormalities are useful predictors only in those with JSN = 0. Intervention studies to prevent radiographic progression probably should utilize joints where evidence of abnormality already exists. At a clinical level, current radiographic status predicts future status, with 50% of patients with JSN = 1 and 50% of patients with JSN = 2 progressing to complete joint space loss in 12.03 and 7.44 years, respectively.

Age Factors↗
PubMed2002

Radiographic methods in knee osteoarthritis: a further comparison of semiflexed (MTP), schuss-tunnel, and weight-bearing anteroposterior views for joint space narrowing and osteophytes.

OBJECTIVE: Current radiographic evaluation of knee osteoarthritis (OA) depends primarily on the presence and severity of joint space narrowing (JSN) and osteophytes. Radiographic JSN is a function of the actual JSN caused by articular cartilage loss and the observable JSN artifactually caused when the tibial and femoral surfaces diverge due to variations in patient's knee position. Views yielding the greatest JSN are the most accurate. Osteophytes are also dependent on positioning. This study investigated the consequences of positioning on JSN and osteophytes in clinical studies in which the outcome of OA knee is scored. METHODS: In total, 1105 patients underwent 1175 paired radiographic examinations using weight-bearing (WB) standard anterior-posterior (AP) extended knee views (AP-WB), semiflexed WB posterior-anterior views with the knee in contact with the film and the 1st metatarsophalangeal (MTP) joint under the film plane (MTP) (method of Buckland-Wright), and WB PA views with the tip of the great toe at the film plane, 20 degrees of knee flexion and 5 degrees downward angulation of the x-ray tube (schuss-tunnel view). Careful attention was given to proper positioning. JSN and osteophytes were scored on a 0-3 scale. RESULTS: JSN was significantly greater by the MTP and schuss-tunnel methods than by the AP-WB method, but no difference was found between the MTP and schuss-tunnel methods. In addition, disagreement was identified in 34% of MTP and AP-WB scores. In 69.3% of disagreements the scores were more abnormal in the MTP view. When the disagreements were studied, the mean MTP score was 1.68 compared to 1.12 for the AP-WB score. Fifty-seven knees were scored as 3 by the MTP view and as 2 by the AP-WB, and 8 knees were scored as 3 by the AP-WB view and 2 by the MTP view. Little difference in osteophytes was noted among the 3 methods, although fewer osteophytes were identified by the schuss-tunnel method than the AP-WB method. CONCLUSION: Using the clinical reading methods of this study, the MTP and schuss-tunnel views were equivalent when compared to each other. When compared with the AP-WB view, the schuss-tunnel view resulted in a lower osteophyte score. These results, based on clinical readings, are similar to previous computerized analyses that indicated that the MTP and schuss-tunnel views were superior to the AP-WB, but that the MTP view was superior to the schuss-tunnel view.

Arthrography↗