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P-glycoprotein is expressed in the mineralizing regions of the skeleton
D C Mangham1, A Cannon, S Komiya
1Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114, USA.
Abstract:
Using oligonucleotide primers specific for the human MDR 1 gene, we were able to identify a specific amplicon using RT-PCR from total bovine growth plate chondrocyte RNA. The identification of MDR mRNA in growth plate chondrocytes led us to examine the precise distribution of MDR P-glycoprotein in bone and cartilage. We applied two monoclonal antibodies (C219 and C494) to human fetal, neonatal, and childhood growth plates and bone. In growth plates, P-glycoprotein was detected at high levels in a perilacunar distribution in the calcifying zone and at lower levels in hypertrophic, but not proliferative or reserve zone, chondrocytes. P-glycoprotein was also observed in perichondrial chondrocytes, in perivascular chondrocytes and matrix in the fetal cartilage anlage, and in osteoblasts and the surface osteoid matrix of newly formed bone trabeculae in the primary spongiosa. The recently described chloride channel of P-glycoprotein suggests a potential role of P-glycoprotein in growth plate chondrocyte hypertrophy.
Insights
Multidrug resistance (MDR) P-glycoprotein is present in bovine growth plate chondrocytes, suggesting a role in chondrocyte hypertrophy and bone development.
Area of Science:
- Biochemistry
- Cell Biology
- Skeletal Biology
Background:
- The multidrug resistance (MDR) gene 1 (MDR1) encodes P-glycoprotein, a transmembrane efflux pump.
- P-glycoprotein's role in skeletal development, particularly in growth plate chondrocytes, is not well understood.
Purpose of the Study:
- To investigate the presence and distribution of MDR P-glycoprotein in bovine growth plate chondrocytes.
- To examine the precise localization of P-glycoprotein within human fetal, neonatal, and childhood growth plates and bone.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was used to detect MDR1 mRNA in bovine chondrocytes.
- Immunohistochemistry with monoclonal antibodies (C219 and C494) was applied to human growth plate and bone tissues.
Main Results:
- MDR1 mRNA was identified in bovine growth plate chondrocytes.
- P-glycoprotein was detected in human growth plates, primarily in the calcifying and hypertrophic zones of chondrocytes.
- P-glycoprotein was also found in perichondrial and perivascular chondrocytes, osteoblasts, and osteoid matrix.
Conclusions:
- MDR P-glycoprotein is expressed in growth plate chondrocytes and associated bone tissues.
- The distribution suggests a potential role for P-glycoprotein in chondrocyte hypertrophy and bone formation.