Premium
Consequences of the loss of collagen XXIV in bone (922.7)
Author(s) -
Gordon Marion,
Jeon Jae Yoon,
Zhou Peihong,
Hahn Rita,
Svoboda Kathy,
Ramirez Francesco
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.922.7
Subject(s) - messenger rna , osteoprotegerin , rankl , resorption , medicine , endocrinology , hydroxyproline , collagen, type i, alpha 1 , femur , type i collagen , chemistry , runx2 , glyceraldehyde 3 phosphate dehydrogenase , andrology , gene expression , surgery , extracellular matrix , biochemistry , activator (genetics) , gene , receptor
Fibrillar collagens give integrity and tensile strength to many organs in the body. Collagen XXIV is a non‐traditional collagen in the fibrillar collagen family. To determine what its function might be in bone, collagen XXIV knock out (KO) mice were analyzed. Since femurs of null mice at 3 and 5 months of age were found to be osteoporotic compared to WT mice, our goal was to quantify mRNAs involved in regulation of bone deposition and resorption, and determine whether the loss of collagen XXIV affected their expression. Femur RNA was extracted from WT and KO mice at 7 days, 1 month, 2 months, 3 months, 6 months, 1 year and 1.5 years of age. RNA was converted to cDNA, and real time qPCR was performed using GAPDH as a control. In WT mice, collagen XXIV mRNA was high at 7 d and 1 month of age. At 2 months it was present at less than half of what it was at 1 month. By 3 months its levels were greatly attenuated. This trend continued for all ages up to 1.5 yrs. KO mice showed minor amounts of collagen XXIV mRNA at 7d, 1 month and 2 months of age, with essentially no transcribed product by 3 months and beyond. Expression levels of RANKL, Runx2, and Lrp5 were elevated in the KO mice. For RANKL, values were 1.7 to 2 fold higher in the KO mouse femurs at all ages except at 2 months, where it was 3.2 times higher. Runx2 mRNA levels were always ~2 to 5 fold higher, except at 1 month of age, where it was ~10 times higher. Lrp5 was ~1.6 to 3.5 times higher in KO mouse femurs than in WT femurs. In summary, seven day old and 1 month old WT mice had the highest expression levels of collagen XXIV mRNA. By 2 months of age, expression was halved, and by 3 months it became negligible. The higher expression of RANKL in KO mice may be responsible for the observed osteoporosis at 3 and 5 months of age. Higher levels of Lrp5 and Runx2 may represent a compensatory mechanism to stimulate bone growth.