Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a rapid reversal in maternal skeletal metabolism and bone remodeling from accelerated bone resorption during lactation to skeletal rebuilding after lactation. The purpose was to determine the changes that occur in maternal osteoclasts during the transition from lactation to postlactation. Skeletal samples were taken from female rats on days 10 and 19 of lactation and 1 and 7 days after lactation. The pups were weaned on day 20. There was a rapid change in the osteoclast population after weaning, resulting in less resorption surface. Osteoclasts detached from bone surfaces, lost their ruffled borders, and became fragmented with immunocytochemical evidence of apoptosis within 24 hr after lactation. Concomitant with the rapid regression in the osteoclast population was an over fivefold increase in maternal calcitonin (CT) levels at 24 hr after weaning. Serum calcium and estrogen (E2) increased, but prolactin (PRL) and PTH decreased after weaning. The hormone changes, particularly that of CT, are consistent with the rapid regression of the osteoclast population at the end of lactation. These changes are similar to a reversal phase of a bone remodeling cycle where bone formation commences when resorption ceases on bone surfaces and suggests that the fate of osteoclasts during bone remodeling is programmed cell death. These results also suggest that bone remodeling is well synchronized prior to, during, and after lactation to accommodate the mineral requirements of the offspring as well as the mother.
Anat Rec (Hoboken) 2007 Jan
PMID:Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during the bone remodeling reversal at the end of lactation. 1744 Nov 99

Parathyroid hormone (PTH; 10(-7) to 10(-15) M) decreased terminal chondrogenesis in the avian sterna. During the first half of an 8-day culture, 100 nM PTH (1-34) significantly increased sternal length and downregulated the deposition of type X collagen and its mRNA expression. However, it remains unclear how PTH increased cartilaginous growth. In this study, we examined growth by both cell proliferation and analysis of cyclin d1 and collagen mRNA. Types II, IX, and X collagens and cyclin d1 mRNA were quantified through real-time RT-PCR, while Ki-67 was used as an immunohistochemical proliferation marker. Extracellular matrix content was measured through mRNA quantification of types II, IX, and X collagen and observing deposition of the same collagens. PTH significantly increased the proliferation marker Ki-67 in the sternal cephalic region. There was less type II and X collagen in PTH-treated sterna with concomitant decreases in mRNA production, suggesting that proliferation was the major contributor to cartilage growth in the presence of PTH/PTH-related peptide receptor activation. In conclusion, these experiments demonstrated that PTH increased cartilage growth by upregulating cell proliferation or other extracellular matrix components.
Anat Rec (Hoboken) 2007 Feb
PMID:Parathyroid hormone/parathyroid hormone-related peptide modulates growth of avian sternal cartilage via chondrocytic proliferation. 1744 Dec 8

Type X collagen (Col-X) deposition is a marker of terminal differentiation during chondrogenesis, in addition to appositional growth and apoptosis. The parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor, or PPR, is a G-Protein coupled receptor (GPCR), which activates several downstream pathways, moderating chondrocyte differentiation, including suppression of Col-X deposition. An Avian sterna model was used to analyze the PPR GPCR downstream kinase role in growth rate and extracellular matrix (ECM) including Col-II, IX, and X. Phosphatidylinositol kinase (PI3K), mitogen activating protein kinase (MAPK) and protein kinase A (PKA) were inhibited with specific established inhibitors LY294002, PD98059, and H89, respectively to test the hypothesis that they could reverse/inhibit the PTH/PTHrP pathway. Excised E14 chick sterna were PTH treated with or without an inhibitor and compared to controls. Sternal length was measured every 24 hr. Cultured sterna were immuno-stained using specific antibodies for Col-II, IX, or X and examined via confocal microscopy. Increased growth in PTH-treated sterna was MAPK, PI3K, and PKA dose dependent, suggesting growth was regulated through multiple pathways. Col-X deposition was rescued in PTH-treated sterna in the presence of PI3K or MAPK inhibitors, but not with the PKA inhibitor. All three inhibitors moderately disrupted Col-II and Col-IX deposition. These results suggest that PTH can activate multiple pathways during chondrocyte differentiation.
Anat Rec (Hoboken) 2010 Feb
PMID:PTH stimulated growth and decreased Col-X deposition are phosphotidylinositol-3,4,5 triphosphate kinase and mitogen activating protein kinase dependent in avian sterna. 1995 41