acid-phosphatase and Osteosclerosis

Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeostasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, immunohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the osteocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogenesis.

Topics: Acid Phosphatase; Aged; Apoptosis; Bone Remodeling; Cell Count; Cell Shape; Female; Gene Expression Profiling; Humans; Isoenzymes; Male; Matrix Metalloproteinases; Microscopy, Electron, Scanning; Middle Aged; Osteoarthritis, Knee; Osteocytes; Osteosclerosis; Phenotype; Real-Time Polymerase Chain Reaction; Staining and Labeling; Tartrate-Resistant Acid Phosphatase

Breast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.. The effects of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.. In vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)(2)D(3) inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49±0.08 mm(2) versus 1.68±0.15 mm(2), P<0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81±0.13 mm(2) versus 0.52±0.11 mm(2) in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.. Vitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.

Topics: Acid Phosphatase; Adipose Tissue; Animals; Apoptosis; Bone and Bones; Bone Neoplasms; Bone Remodeling; Breast Neoplasms; Calcitriol; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Mice; Osteolysis; Osteosclerosis; Radiography; Tartrate-Resistant Acid Phosphatase; Tumor Burden; Vitamin D Deficiency; Xenograft Model Antitumor Assays

Pycnodysostosis (Pycno) is an autosomal recessive osteosclerotic skeletal dysplasia that is caused by the markedly deficient activity of cathepsin K. This lysosomal cysteine protease has substantial collagenase activity, is present at high levels in osteoclasts, and is secreted into the subosteoclastic space where bone matrix is degraded. In vitro studies revealed that mutant cathepsin K proteins causing Pycno did not degrade type I collagen, the protein that constitutes 95% of organic bone matrix. To determine the in vivo effects of cathepsin K mutations on bone metabolism in general and osteoclast-mediated bone resorption specifically, several bone metabolism markers were assayed in serum and urine from seven Pycno patients. Two markers of bone synthesis, type I collagen carboxy-terminal propeptide and osteocalcin, were normal in all Pycno patients. Tartrate-resistent acid phosphatase, an osteoclast marker, was also normal in these patients. Two markers that detect type I collagen telopeptide cross-links from the N and C termini, NTX and CTX, respectively, were low in Pycno. A third marker which detects a more proximal portion of the C terminus of type I collagen in serum, ICTP, was elevated in Pycno, a seemingly paradoxical result. The finding of decreased osteoclast-mediated type I collagen degradation as well as the use of alternative collagen cleavage sites by other proteases, and the accumulation of larger C-terminal fragments containing the ICTP epitope, established a unique biochemical phenotype for Pycno.

Topics: Acid Phosphatase; Adolescent; Adult; Amino Acids; Biomarkers; Bone and Bones; Bone Matrix; Cathepsin K; Cathepsins; Child; Collagen; Collagen Type I; Humans; Isoenzymes; Mutagenesis; Osteocalcin; Osteosclerosis; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

In a co-culture system of mouse spleen cells and osteoblastic cells, we have demonstrated that a suitable microenvironment must be provided by osteoblastic cells in order for osteoclast-like multinucleated cell (MNC) formation. Using this co-culture system, we examined the pathogenetic mechanism underlying the lack of bone resorption in osteosclerotic oc/oc mice. Numerous tartrate-resistant acid phosphatase (TRAP, an osteoclast marker enzyme)-positive MNCs were formed in response to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] both in co-cultures of oc/oc spleen cells and normal osteoblastic cells and in those of normal spleen cells and oc/oc osteoblastic cells. TRAP-positive MNCs derived from normal spleen cells tended to spread out on culture dishes, whereas those from oc/oc spleen cells remained as small, compact MNCs. When TRAP-positive MNCs enriched from co-cultures of normal spleen cells and oc/oc osteoblastic cells were cultured on dentine slices, they formed numerous resorption pits with ruffled borders and clear zones. In contrast, none of the TRAP-positive MNCs derived from oc/oc spleen cells formed either ruffled borders or resorption pits. These results indicate that the lack of bone resorption in oc/oc mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells.

Topics: Acid Phosphatase; Animals; Animals, Newborn; Biomarkers; Bone Resorption; Calcitonin; Calcitriol; Cell Communication; Cells, Cultured; Mice; Mice, Mutant Strains; Osteoblasts; Osteoclasts; Osteosclerosis; Spleen

Acute megakaryoblastic leukemia or acute "malignant" myelosclerosis is an acute and rapidly progressive myeloproliferative syndrome characterized by minimal or absent splenomegaly, pancytopenia, diffuse marrow fibrosis, and circulating blasts of megakaryocytic origin. The disease must be differentiated from other hematologic malignancies especially myelofibrosis with myeloid metaplasia. The radiographic changes of osteosclerosis in our patient have not been previously reported in the literature.

Topics: Acid Phosphatase; Acute Disease; Hemoglobinometry; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Osteosclerosis; Primary Myelofibrosis; Radiography

Morphokinetic measurements after tetracycline labeling were performed on bone specimens of the iliac crest in a 30-year-old man and a 38-year-old women. On radiographs, the osteopetrosis (=marble bone disease Albers-Schönberg) was characterized by an almost homogenous osteosclerosis in the man and by variable zones of high and normal density in the woman. Histologically, the man revealed increased rates of bone formation and mineralisation as signs of hyperactivity of the osteoblasts accompanied, biochemically, by an elevation of serum alkaline phosphatase and a high urinary output of hydroxyproline. In the woman increased resorbing bone seams, and elevation of serum acid phosphatase and a slightly lowered urinary output of hydroxyproline were apparent as signs of an osteoclastic deficiency. The cause of osteopetrosis has been generally ascribed to decreased bone resorption. This study shows that the accumulation of bone mass in osteopetrosis may be due also to increased bone formation and that by pathomechanism, probably, two forms of osteopetrosis in the adult may be differentiated.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Female; Humans; Hydroxyproline; Male; Osteopetrosis; Osteosclerosis; Radiography

Topics: Acid Phosphatase; Acute Disease; Adult; Cell Differentiation; Esterases; Histocytochemistry; Humans; Leukemia; Male; Naphthaleneacetic Acids; Osteosclerosis; Primary Myelofibrosis; Staining and Labeling

Topics: Absorptiometry, Photon; Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Blood Urea Nitrogen; Calcium; Creatinine; Female; Humans; Male; Middle Aged; Osteosclerosis; Pedigree; Phosphorus; Potassium; Radiography, Thoracic; Skull

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Diethylstilbestrol; Drug Therapy; Enzyme Inhibitors; Geriatrics; Humans; Male; Neoplasm Metastasis; Neoplasms; Osteosclerosis; Pathology; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Radiography; Tartrates

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteogenesis Imperfecta; Osteopetrosis; Osteosclerosis; Prostatic Neoplasms