Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis Type II — a family study

Yoneyama, Tatsuo; Fowler, Hilton L.; Pendleton, John W.; Sforza, Peter P.; R, Gérard; Lui, Charles Y.; Eldridge, Thomas H.; Iranmanesh, A.

doi:10.1111/j.1399-0004.1992.tb03134.x

Cited by 16 publications

(7 citation statements)

References 17 publications

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“…Of interest, at basal level (t 0 ), we found an inverse correlation between serum Ckbb and CTx, a biochemical parameter considered a reliable indicator of in vivo osteoclast activity representing one of the end products of bone matrix resorption. This result reinforces the hypothesis that the determination of serum Ckbb could be considered as a new molecular target for osteoclast failure (10,11). Nevertheless, after the first infusion, no significant correlation was still present between these two parameters.…”

Section: Discussionsupporting

confidence: 87%

“…This patient had a normal serum Ckbb when he was reevaluated 6 y later, showing that his osteoclasts resumed functioning (18). These findings suggest that elevated serum Ckbb reflects a fundamental disturbance in osteoclast biology, so that the authors proposed it as a potential marker of osteoclast failure although the mechanisms involved remain unclear (10,11).…”

Section: Discussionmentioning

confidence: 82%

“…Previous clinical studies reported elevated serum level of Ckbb in patients with OPT (even clinically mild types) in which osteoclastic dysfunction is the cardinal pathogenetic factor (8)(9)(10)(11). In addition to genetic OPT, elevated serum Ckbb has been reported in acquired OPT in a 12-y-old boy with idiopathic bone pain and treated with very high doses of BP (pamidronate) over a period of 2 y (12).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, elevation of serum levels of Ckbb has been found in some types of osteopetrosis (OPT) in which osteoclasts fail to resorb bone (8)(9)(10). Moreover, a study examining patients with the most common clinical forms of OPT and patients with other sclerosing bone disorders found that the presence of Ckbb in serum seemed to distinguish true OPT (11).…”

mentioning

confidence: 99%

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Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment

et al. 2014

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment

et al. 2014

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“…In humans, elevation of serum levels of Ckb has been found in patients with type 2 autosomal dominant osteopetrosis. The patients have increased osteoclasts without any bone resorption activity (35,36). The present studies determined the molecular mechanisms underlying the regulation of Ckb in osteoclasts, which may shed light on a molecular mechanism of the elevation in serum levels of Ckb in these osteopetrosis patients with increased osteoclasts.…”

Section: Discussionmentioning

confidence: 97%

RANKL Up-regulates Brain-type Creatine Kinase via Poly(ADP-ribose) Polymerase-1 during Osteoclastogenesis

Chen

Sun

Mao

et al. 2010

Journal of Biological Chemistry

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Receptor activator of nuclear factor B ligand (RANKL) is the key regulator for osteoclast formation and function. During osteoclastogenesis, RANKL-stimulated signals differentially modulate expression of a large number of proteins. Using proteomics approaches, we identified that brain-type cytoplasmic creatine kinase (Ckb) was greatly induced in mature osteoclasts. Ckb has been shown to contribute to osteoclast function. However, the mechanisms of Ckb regulation and the contribution of other isoforms of creatine kinase during RANKL-induced osteoclastogenesis are unknown. We found that Ckb was the predominant isoform of creatine kinase during osteoclastogenesis. Real-time PCR confirmed that RANKL induced ckb mRNA expression by over 40-fold in primary mouse bone marrow macrophages and Raw 264.7 cells. The RANKL-responsive region was identified within the ؊0.4-to ؊0.2-kb 5-flanking region of the ckb gene. Affinity binding purification followed by mass spectrometry analysis revealed that poly(ADP-ribose) polymerase-1 (PARP-1) bound to the ؊0.4/؊0.2-kb fragment that negatively regulated expression of ckb in response to RANKL stimulation. Electrophoretic mobility shift assays with PARP-1-specific antibody located the binding site of PARP-1 to the TTCCCA consensus sequence. The expression of PARP-1 was reduced during RANKL-induced osteoclastogenesis, concurrently with increased expression of Ckb. Consistently, knockdown of PARP-1 by lentivirus-delivered shRNA enhanced ckb mRNA expression. The activity of PARP-1 was determined to be required for its inhibitory effect on the ckb expression. In summary, we have demonstrated that PARP-1 is a negative regulator of the ckb expression. Down-regulation of PARP-1 is responsible for the up-regulation of ckb during RANKL-induced osteoclastogenesis.

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Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders

Whyte

Chines

Silva

et al. 1996

Journal of Bone and Mineral Research

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Creatine kinase (CK) isoenzyme BB-CK is predominantly found in brain and is not normally detected in the blood. A few recent reports, however, have described BB-CK in serum from several patients with osteopetrosis (OP). To evaluate the presence and specificity of BB-CK in serum in the osteopetroses among disorders that increase skeletal mass, we quantitated total CK activity and CK isoenzymes in 15 patients representing the five major clinical forms of OP (2 infantile, 3 intermediate, 7 adult [2 type I, 5 type II], and 3 carbonic anhydrase II [CA II] deficiency cases) and in 22 patients representing 14 other types of sclerosing bone disease. All OP patients (except the two adult type I subjects) had BB-CK readily detected in their serum. Conversely, only 1 of the 22 patients with other sclerosing bone disorders had detectable BB-CK in serum (1 of 3 patients with fibrodysplasia [myositis] ossificans progressiva who had barely measurable activity). In three OP patients (one of two with the infantile form and two of five with adult, type II disease), BB-CK values were sufficiently high that serum total CK activity was elevated. In a newborn with malignant OP, both cord blood plasma and peripheral blood serum had substantial amounts of BB-CK. In three subjects (with adult type II OP), who were restudied 2-6 years later, BB-CK was still elevated in their blood. BB-CK in serum appears to distinguish the osteopetroses among the sclerosing bone disorders. Absence of serum BB-CK in adult type I disease suggests that this condition may not be a genuine form of OP. Assay of BB-CK in fetal blood could be studied as a means for prenatal diagnosis of malignant OP. Why the osteoclast failure that characterizes all true forms of OP is associated with BB-CK in the circulation is a new question for skeletal biologists.

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Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis Type II — a family study

Cited by 16 publications

References 17 publications

Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment

Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment

RANKL Up-regulates Brain-type Creatine Kinase via Poly(ADP-ribose) Polymerase-1 during Osteoclastogenesis

Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders

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