Me: This is one of those posts that is more for information and to help the reader (and me) to better understand the various endocine and molecular biological pathways and functions. From the two studies below, we see that leptin is needed for this list of functions
- 1. increase in femur and humerus length
- 2. decrease in length of the calcified zone hypertrophic zone relative to the entire hypertrophic zone. (which is a good thing)
- 3. increased organized collagen fibril arrangement
- 4. modulates several events associated with terminal differentiation of chondrocytes
- 5. altered type X collagen mRNA expression (Type X Collagen is produced by the chondrocytes in the hypertropic layer)
- 6. suppressed apoptosis, cell growth and matrix calcification
- 7. acts on human marrow stromal cells to enhance differentiation into osteoblasts and inhibit differentiation into adipocytes
- 8. inhibits bone formation through a hypothalamic relay
- 9. High expression of leptin was identified in hypertrophic chondrocytes in the vicinity of capillary blood vessels invading hypertrophic cartilage
- 10. Leptin enhanced the proliferation, migration, tube formation, and matrix metalloproteinase-2 (MMP-2) activity of human endothelial cells
- 11. leptin exerts its influence on endochondral ossification by regulating angiogenesis (creation of blood vessels) (The hypertrophic chondrocytes far from the blood vessels were negative for leptin)
From Source Link HERE
Bone. 2005 Nov;37(5):607-21. Epub 2005 Jul 20.
Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification.
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Japan.
Leptin has been suggested to mediate a variety of actions, including bone development, via its ubiquitously expressed receptor (Ob-Rb). In this study, we investigated the role of leptin in endochondral ossification at the growth plate. The growth plates of wild-type and ob/ob mice were analyzed. Effects of leptin on chondrocyte gene expression, cell cycle, apoptosis and matrix mineralization were assessed using primary chondrocyte culture and the ATDC5 cell differentiation culture system. Immunohistochemistry and in situ hybridization showed that leptin was localized in prehypertrophic chondrocytes in normal mice and that Ob-Rb was localized in hypertrophic chondrocytes in normal and ob/ob mice. Growth plates of ob/ob mice were more fragile than those of wild-type mice in a mechanical test and were broken easily at the chondro-osseous junction. The growth plates of ob/ob mice showed disturbed columnar structure, decreased type X collagen expression, less organized collagen fibril arrangement, increased apoptosis and premature mineralization. Leptin administration in ob/ob mice led to an increase in femoral and humeral lengths and decrease in the proportional length of the calcified hypertrophic zone to the whole hypertrophic zone. In primary chondrocyte culture, the matrix mineralization in ob/ob chondrocytes was stronger than that of wild-type mice; this mineralization in both types of mice was abolished by the addition of exogenous leptin (10 ng/ml). During ATDC5 cell differentiation culture, exogenous leptin at a concentration of 1-10 ng/ml (equivalent to the normal serum concentration of leptin) altered type X collagen mRNA expression and suppressed apoptosis, cell growth and matrix calcification. In conclusion, we demonstrated that leptin modulates several events associated with terminal differentiation of chondrocytes. Our finding that the growth plates of ob/ob mice were fragile implies a disturbance in the differentiation/maturation process of growth plates due to depletion of leptin signaling in ob/ob mice. These findings suggest that peripheral leptin signaling plays an essential role in endochondral ossification at the growth plate.
Source Link HERE
J Histochem Cytochem. 2002 Feb;50(2):159-69.
Potential role of leptin in endochondral ossification.
First Department of Oral and Maxillofacial Surgery, School of Dentistry, The University of Tokushima, Tokushima, Japan.
Leptin, a 16-kD circulating hormone secreted mainly by white adipose tissue, is a product of the obese (ob) gene. Leptin acts on human marrow stromal cells to enhance differentiation into osteoblasts and inhibit differentiation into adipocytes. Leptin also inhibits bone formation through a hypothalamic relay. To obtain a better understanding of the potential role of leptin in bone formation, the localization of leptin in endochondral ossification was examined immunohistochemically. High expression of leptin was identified in hypertrophic chondrocytes in the vicinity of capillary blood vessels invading hypertrophic cartilage and in a number of osteoblasts of the primary spongiosa beneath the growth plate. The hypertrophic chondrocytes far from the blood vessels were negative for leptin. Moreover, we detected the production and secretion of leptin by a mouse osteoblast cell line (MC3T3-E1) and a mouse chondrocyte cell line (MCC-5) by RT-PCR, immunocytochemistry, and Western blotting. Leptin enhanced the proliferation, migration, tube formation, and matrix metalloproteinase-2 (MMP-2) activity of human endothelial cells (HUVECs) in vitro. These findings suggest the possibility that leptin exerts its influence on endochondral ossification by regulating angiogenesis.
- PMID: 11799135 [PubMed – indexed for MEDLINE]