Article

Metabolic activation stimulates acid secretion and expression of matrix degrading proteases in human osteoblasts

Otto-von-Guericke-Universität Magdeburg, Magdeburg, Saxony-Anhalt, Germany
Annals of the Rheumatic Diseases (Impact Factor: 10.38). 02/2004; 63(1):67-70. DOI: 10.1136/ard.2002.005256
Source: PubMed

ABSTRACT Both cellular and matrix components of healthy bone are permanently renewed in a balanced homoeostasis. Osteoclastic bone resorption involves the expression of vacuolar-type ATPase proton pumps (vATPase) on the outer cell membrane and the secretion of matrix degrading proteases. Osteoblasts modulate the deposition of bone mineral components and secrete extracellular matrix proteins.
To investigate the ability of osteoblasts and osteosarcoma to secrete acid and express matrix degrading proteases upon metabolic activation. To examine also the potential contribution of vATPases to proton secretion expressed on osteoblasts.
Osteoblasts were isolated from trabecular bone and characterised by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Proton secretion was analysed by a cytosensor microphysiometer.
Osteoblasts not only express matrix degrading proteases upon stimulation with tumour necrosis factor or with phorbol ester but they also secrete protons upon activation. Proton secretion by osteoblasts is associated partially with proton pump ATPases.
These data suggest that, in addition to monocyte derived osteoclasts, cytokine activated mesenchymal osteoblasts and osteosarcoma cells may contribute to the acidic milieu required for bone degradation.

0 Followers
 · 
91 Views
  • Source
    • "Thus, the increased serum osteoprotegerin levels in humans may reflect a compensatory response against enhanced osteoclastic bone resorption and the resultant loss of bone. In this respect, our data suggest that osteoblast-like cells may also participate in organic matrix degradation during remodeling cycle by producing collagenolytic cathepsin K. Osteoblasts, although their number may be reduced in osteoporotic patients, cover trabeculae and are able to locally decrease extracellular pH [37], a requirement for optimal cathepsin K activity for collagen degradation. It must also be noted that the slight but detectable progressive metabolic acidosis during ageing [38] [39] may contribute to bone surface demineralization seen in patients with osteoporosis [34]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H(+)-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine proteinases. Recently, it has been shown that osteoblasts may contribute to organic matrix remodeling. We therefore investigated their ability to produce cathepsin K for this action. Trabecular bone samples were collected from patients operated due to a fracture of the femoral neck. Part of the bone was decalcified and the rest was used for cell isolation. Sections from the decalcified bone were immunostained with antibodies against cathepsin K. Isolated cells were characterized for their ability to form mineralized matrix and subsequently analyzed for their cathepsin K production by Western blotting and quantitative RT-PCR. Osteoblasts, bone lining cells and some osteocytes in situ showed cathepsin K immunoreactivity and osteoblast-like cells in vitro produced cathepsin K mRNA and released both 42 kDa pro- and 27 kDa processed cathepsin K to culture media. Osteoblastic cathepsin K may thus contribute to collagenous matrix maintenance and recycling of improperly processed collagen I. Whether osteoblastic cathepsin K synthesis has consequences in diseases characterized by abnormal bone matrix turnover remains to be investigated.
    Bone 07/2006; 38(6):769-77. DOI:10.1016/j.bone.2005.10.017 · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current study tests the hypothesis that basal level and minute-by-minute correction of plasma Ca2+ by outward and inward Ca2+ fluxes from and into an exchangeable ionic pool in bone is controlled by an active partition system without contributions from the bone remodeling system. Direct real-time measurements of Ca2+ fluxes were made using the scanning ion-selective electrode technique (SIET) on living bones maintained ex vivo in physiological conditions. SIET three-dimensional measurements of the local Ca2+ concentration gradient (10 microm spatial resolution) were performed on metatarsal bones of weanling mice after drilling a 100-mum hole through the cortex to expose the internal bone extracellular fluid (BECF) to the bathing solution, whose composition mimicked the extracellular fluid (ECF). Influxes of Ca2+ towards the center of the cortical hole (15.1+/-4.2 pmol cm-2 s-1) were found in the ECF and were reversed to effluxes (7.4+/-2.9 pmol cm-2 s-1) when calcium was depleted from the ECF, mimicking a plasma demand. The reversal from influx to efflux and vice versa was immediate and fluxes in both directions were steady throughout the experimental time (>or=2 h, n=14). Only the efflux was nullified within 10 min by the addition of 10 mM/L Na-Cyanide (n=7), demonstrating its cell dependence. The timeframes of the exchanges and the stability of the Ca2+ fluxes over time suggest the existence of an exchangeable calcium pool in bone. The calcium efflux dependency on viable cells suggests that an active partition system might play a central role in the short-term error correction of plasma calcium without the contribution of bone remodeling.
    Bone 10/2005; 37(4):545-54. DOI:10.1016/j.bone.2005.04.036 · 4.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die juvenile Dermatomyositis ist eine idiopathische entzndliche Multisystemerkrankung, charakterisiert durch eine chronische Entzndung der Skelettmuskulatur mit kutanen und vaskulitischen Manifestationen. Die Behandlung mit Kortikosteroiden und Immunsuppressiva stellt einen aktuellen Standard dar. Die Verfgbarkeit einer spezifischen antientzndlichen Intervention mit Biologika und die Toxizitt der konventionellen Therapie lassen Behandlungsversuche mit Ersteren, insbesondere bei therapierefraktren Verlufen, als sinnvoll erscheinen. Dabei sind v.a. Inhibitoren des proinflammatorischen Zytokins Tumornekrosefaktor , Etanercept und Infliximab, und der B-Zell-depletierende Antikrper Rituximab eingesetzt worden. In dieser bersicht sollen die derzeitigen Therapieerfahrungen dargestellt werden.Juvenile dermatomyositis is an idiopathic, inflammatory, multi-systemic disease characterized by a chronic inflammation of skeletal muscles with cutaneous and vasculitic manifestations. Treatment with corticosteroids and immunosuppressants has become standard. The availability of specific anti-inflammatory biological agents and the toxicity of conventional therapy have led to therapeutic trials using such agents, especially in refractory disease. Inhibitors of the proinflammatory cytokine tumour necrosis factor-, etanercept and infliximab, and the B-cell depleting antibody rituximab have been used. In this report, our current knowledge of treatment of juvenile dermatomyositis using biologicals is reviewed.
    Monatsschrift Kinderheilkunde 02/2007; 155(2):111-117. DOI:10.1007/s00112-006-1453-x · 0.28 Impact Factor
Show more