scholarly journals Sotrastaurin, a PKC inhibitor, attenuates RANKL‐induced bone resorption and attenuates osteochondral pathologies associated with the development of OA

2020 ◽  
Vol 24 (15) ◽  
pp. 8452-8465 ◽  
Author(s):  
Cong Pang ◽  
Liangbao Wen ◽  
Haikuo Qin ◽  
Bikang Zhu ◽  
Xuanyuan Lu ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Pkc Inhibitor

Protein kinase C affects microfilaments, bone resorption, and [Ca2+]o sensing in cultured osteoclasts

1992 ◽  
Vol 263 (1) ◽  
pp. C130-C139 ◽  
Author(s):  
A. Teti ◽  
S. Colucci ◽  
M. Grano ◽  
L. Argentino ◽  
A. Zambonin Zallone
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Bone Resorption ◽  
Calcium Concentration ◽  
Free Calcium ◽  
Rhodamine Phalloidin ◽  
Pkc Inhibitor ◽  
Osteoclast Activity ◽  
Kinase C ◽  
Long Term Treatment

The effects of protein kinase C (PKC) in the control of osteoclast activity are still unknown. We investigated the role of the enzyme in the control of microfilament organization, podosome assembly, bone resorption, and extracellular Ca2+ sensing in chicken and rabbit osteoclasts treated with agents known to affect PKC activity. Cells were treated for 20 min with a PKC activator [phorbol 12-myristate 13-acetate (PMA)], a PKC inhibitor (staurosporine), a protein kinase A (PKA) inhibitor (H-9), a guanosine 3',5'-cyclic monophosphate-dependent protein kinase-PKA-PKC inhibitor (H-7), or with the inactive phorbol, 4 alpha-phorbol, to examine microfilaments by decoration with rhodamine-phalloidin. In PMA-treated osteoclasts, the number of microfilament-containing adhesion structures (podosomes) per cell decreased. However, enlarged microfilamentous cores in podosomes and stress fiber-like filaments, otherwise absent in controls, appeared. Whereas H-7 induced increase of the number of podosomes, staurosporine, H-9, and 4 alpha-phorbol failed to change microfilament organization. Chicken osteoclasts received also long-term treatment with the agents in the presence of [3H]proline-prelabeled chicken or rat bone particles to measure bone resorption. PMA, as well as staurosporine and H-7, stimulated the resorbing activity, whereas cells were insensitive to H-9 and 4 alpha-phorbol. Measurement of cytosolic free calcium concentration in PMA-treated fura-2-loaded single osteoclasts demonstrated a synergistic effect of PKC activation on the inhibitory extracellular calcium concentration-sensing mechanism, which was, by contrast, blocked by H-7, staurosporine, and H-9 and was insensitive to 4 alpha-phorbol. These results indicate that PKC regulates osteoclast activity inducing both morphological and functional modifications.

Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumours associated with the humoral hypercalcaemia of malignancy

1987 ◽  
Vol 114 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Chohei Shigeno ◽  
Itsuo Yamamoto ◽  
Shegiharu Dokoh ◽  
Megumu Hino ◽  
Jun Aoki ◽  
...  
Keyword(s):  
Bone Resorption ◽  
High Performance ◽  
Basic Protein ◽  
Gel Filtration ◽  
Exchange Chromatography ◽  
Protein Factor ◽  
Human Tumours ◽  
Acid Stable ◽  
Bone Resorbing Activity

Abstract. We have partially purified a tumour factor capable of stimulating both bone resorption in vitro and cAMP accumulation in osteoblastic ROS 17/2 cells from three human tumours associated with humoral hypercalcaemia of malignancy. Purification of tumour factor by sequential acid urea extraction, gel filtration and cation-exchange chromatography, reverse-phase high performance liquid chromatography followed by analytical isoelectric focussing provided a basic protein (pI > 9.3) with a molecular weight of approximately 13 000 as a major component of the final preparation which retained both the two bioactivities. Bone resorbing activity and cAMP-increasing activity in purified factor correlated with each other. cAMP-increasing activity of the factor was heat- and acid-stable, but sensitive to alkaline ambient pH. Treatment with trypsin destroyed cAMP-increasing activity of the factor. Synthetic parathyroid hormone (PTH) antagonist, human PTH-(3– 34) completely inhibited the cAMP-increasing activity of the factor. The results suggest that this protein factor, having its effects on both osteoclastic and osteoblastic functions, may be involved in development of enhanced bone resorption in some patients with humoral hypercalcaemia of malignancy.

Polyunsaturated fatty acids and phytoestrogens modulate osteoclastogenesis and bone resorption in raw 264.7 macrophages

2013 ◽  
Author(s):  
Natalie Shepherd ◽  
Jager Cassandre De ◽  
Abe Kasonga ◽  
Sumari Marais ◽  
Yuko Tousen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Bone Resorption ◽  
Polyunsaturated Fatty Acids ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages
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