ABSTRACT
BACKGROUND: Procollagen C-proteinase enhancer 1 (PCPE1), a glycoprotein secreted from differentiating osteoblast, enhances the rate-limiting step of collagen type I fibrillar formation. It is expressed and secreted by cells that produce collagen type I and has the potential to be a marker for bone pathologies. METHODS: We developed an assay to quantify PCPE glycopattern based on isoelectric focusing (IEF) and detection with a bio-imaging camera (coefficient of variation within and between assays, 15% and 20%, respectively). RESULTS: PCPE was quantified in 39 serum samples from healthy subjects (17 females and 22 males). The concentration in the serum was 305(274) ng/ml, median(IQR). The level of the PCPE isoforms and their relative distribution were altered in patients with bone disorders. CONCLUSIONS: The data generated by our system, support our hypothesis that combined data on PCPE concentration and isoforms may be useful for the diagnosis and follow-up of bone diseases. Further research, on larger cohorts of both normal subjects and patients, must be done.
Subject(s)
Carbohydrates/chemistry , Extracellular Matrix Proteins/blood , Glycoproteins/blood , Adult , Bone Diseases, Metabolic/blood , Cell Line , Extracellular Matrix Proteins/chemistry , Female , Glycoproteins/chemistry , Humans , Isoelectric Focusing , Male , Middle Aged , Reference Values , Reproducibility of ResultsABSTRACT
PURPOSE: Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. PATIENTS AND METHODS: Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. RESULTS: Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. CONCLUSION: The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.
Subject(s)
Biomarkers/blood , Bone Density Conservation Agents/adverse effects , Collagen Type I/blood , Diphosphonates/adverse effects , Jaw Diseases/blood , Osteonecrosis/blood , Peptides/blood , Administration, Oral , Adult , Aged , Aged, 80 and over , Alkaline Phosphatase/blood , Bone Density Conservation Agents/administration & dosage , Chi-Square Distribution , Diphosphonates/administration & dosage , Female , Humans , Injections, Intravenous , Jaw Diseases/chemically induced , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Oral Surgical Procedures/adverse effects , Osteonecrosis/chemically induced , Parathyroid Hormone/blood , Predictive Value of Tests , Prospective Studies , Risk Assessment , Young AdultABSTRACT
BACKGROUND: Procollagen C-proteinase (PCP) enhancer 1 (PCPE1) specifically stimulates the PCP activity of bone morphogenic protein 1 (BMP1), a multisubstrate enzyme essential to the formation of extracellular matrix, via direct interaction with its substrate procollagen. Thus, in this study we sought to determine if serum PCPE1 (sPCPE1), a regulator of collagen formation, can be used as a diagnostic marker of collagen metabolism/remodeling. METHODS: We developed a method to track sPCPE1, and the findings were applied to evaluate the association of sPCPE1 glycopatterns with growth and presence of bone complication. RESULTS: Isoelectric focusing revealed that sPCPE1 has a multi-band appearance and that sPCPE1 glycopatterns are due to an N-linked oligosaccharide decorated with sialic acid. Evaluation of PCPE1 glycopatterns in different groups of subjects revealed a significant difference among preterm babies, term babies, and adults. Furthermore, in adults with breast cancer, the glycopattern intensity correlated with the presence of bone metastasis. CONCLUSIONS: The sPCPE1 glycopattern appears to be associated with the physiological and pathological states of bone. This study shows for the first time sPCPE1 glycopattern and suggest that changes in glycosylation of the protein may be in correlation with collagen metabolism. Studies are currently underway to determine its appearance in the serum of normal population on one hand and its appearance during growth and metabolic bone diseases on the other hand.
