PMID- 15207745
OWN - NLM
STAT- MEDLINE
DCOM- 20050819
LR  - 20191210
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 35
IP  - 1
DP  - 2004 Jul
TI  - ACTH enhances chondrogenesis in multipotential progenitor cells and matrix 
      production in chondrocytes.
PG  - 96-107
AB  - The association of melanocortin peptide overproduction with enhanced linear 
      growth prompted the current investigation of adrenocorticotropin hormone (ACTH) 
      effects on multipotential chondroprogenitor populations and committed 
      chondrocytes in culture. Two multipotential progenitor populations, rat bone 
      marrow stromal cells (BMSC) and the clonal multipotential cell line RCJ3.1, and 
      two committed chondrocyte populations, resting chondrocytes (RC) isolated from 
      the rib of young rats and the chondrocyte restricted cell line RCJ3.1C5.18 
      (C5.18), were cultured in differentiation medium plus or minus ACTH. Alcian blue 
      stain was used to quantitate proteoglycan matrix production in all populations 
      treated with a range of ACTH concentrations. Changes in proliferation due to ACTH 
      treatment of all cell types were measured using 3H-thymidine incorporation. 
      Differences in matrix production of ACTH-treated and -untreated RC and C5.18 
      cells were determined using 3H-proline incorporation. Relative transcript 
      expression of the chondrocyte matrix proteins collagen type II (COLL II) and 
      aggrecan (AGR) in treated and untreated cells was analyzed by Northern blot. 
      Collagen type X (COLL X), a marker of hypertrophic differentiation, was measured 
      in committed chondrocytic populations. Western analysis was used to detect the 
      melanocortin-3 receptor (MC3-R), which was a suspected mediator of the ACTH 
      signal. Matrix deposition was dose-dependently increased by ACTH in all cell 
      populations as measured by alcian blue stain. ACTH treatment increased 
      proliferation in multipotential progenitor populations (BMSC and RCJ3.1) while 
      proliferation was decreased in committed chondrocyte populations (RC and C5.18). 
      Total protein and total cell-associated collagen production were significantly 
      increased by ACTH treatment in committed populations. Relative COLL II and AGR 
      transcript expressions were significantly increased in both the RC- and 
      C5.18-committed population and very significantly increased in the progenitor 
      populations. Additionally, collagen type X expression was detected earlier and in 
      greater abundance in ACTH-treated committed chondrocyte populations. Finally, the 
      melanocortin-3 receptor was detected in all examined cell types by Western blot. 
      These data show that ACTH promotes the development of the chondrocyte phenotype 
      from multipotential mesenchymal progenitor populations and increases matrix 
      production and differentiation of committed chondrocytes. These findings, 
      together with the detection of the MC3-R in all of these cell types, indicate a 
      role for the melanocortin system in chondrogenesis.
FAU - Evans, Jodi F
AU  - Evans JF
AD  - Department of Medicine, Winthrop University Hospital, Mineola, NY 11501, USA. 
      jevans@winthrop.org
FAU - Niu, Qing-Tian
AU  - Niu QT
FAU - Canas, J Atilio
AU  - Canas JA
FAU - Shen, Chwan-L
AU  - Shen CL
FAU - Aloia, John F
AU  - Aloia JF
FAU - Yeh, James K
AU  - Yeh JK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Acan protein, rat)
RN  - 0 (Aggrecans)
RN  - 0 (Collagen Type II)
RN  - 0 (Collagen Type X)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptor, Melanocortin, Type 3)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
SB  - IM
MH  - Adrenocorticotropic Hormone/*pharmacology/physiology
MH  - Aggrecans
MH  - Animals
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chondrocytes/*cytology/metabolism
MH  - Chondrogenesis/*drug effects/physiology
MH  - Collagen Type II/genetics/metabolism
MH  - Collagen Type X/biosynthesis/genetics
MH  - Extracellular Matrix/*metabolism
MH  - Extracellular Matrix Proteins/genetics/metabolism
MH  - Female
MH  - Lectins, C-Type
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - Multipotent Stem Cells/*cytology/metabolism
MH  - Proteoglycans/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Melanocortin, Type 3/metabolism
MH  - Stromal Cells/cytology/metabolism
EDAT- 2004/06/23 05:00
MHDA- 2005/08/20 09:00
CRDT- 2004/06/23 05:00
PHST- 2003/12/08 00:00 [received]
PHST- 2004/03/11 00:00 [revised]
PHST- 2004/03/16 00:00 [accepted]
PHST- 2004/06/23 05:00 [pubmed]
PHST- 2005/08/20 09:00 [medline]
PHST- 2004/06/23 05:00 [entrez]
AID - S8756328204001218 [pii]
AID - 10.1016/j.bone.2004.03.015 [doi]
PST - ppublish
SO  - Bone. 2004 Jul;35(1):96-107. doi: 10.1016/j.bone.2004.03.015.