Potential Role of Leptin in Endochondral Ossification

Kume, K.; Satomura, Kimio; Nishisho, Sachiko; Kitaoka, Eiichiro; Yamanouchi, Kouji; Tobiume, Satoru; Nagayama, Masaru

doi:10.1177/002215540205000204

Cited by 118 publications

(90 citation statements)

References 41 publications

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“…The positivity for leptin expression we found in chondrocytes appears to be in line with in vivo and in vitro findings recorded by other authors (Kume et al 2002). Note that chondrocytes have also been found to express leptin receptor (Steppan et al 2000;Figenschau et al 2001;Cornish et al 2002;Kume et al 2002;Gat-Yablonski et al 2004).…”

Section: Discussionsupporting

confidence: 93%

“…Note that chondrocytes have also been found to express leptin receptor (Steppan et al 2000;Figenschau et al 2001;Cornish et al 2002;Kume et al 2002;Gat-Yablonski et al 2004). Because leptin has been observed to be present in synovial fluid and in chondrocytes of articular cartilage of patients affected by osteoarthritis as well as in osteophytes, it has been postulated that leptin might exert a modulatory effect on chondrocyte metabolism and consequently on the pathogenesis of osteoarthritis (Dumond et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, very few in vivo studies have been conducted on the leptin system and they only concern murine fetal and neonatal bone (Hoggard et al 1997;Kume et al 2002). For this reason, the aim of the present immunohistochemical study under light microscopy (LM) was to analyse in vivo leptin expression in cartilage and in bone cells pertaining to the osteogenic lineage of growing rat and adult human bones.…”

Section: Introductionmentioning

confidence: 99%

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In vivo leptin expression in cartilage and bone cells of growing rats and adult humans

et al. 2004

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The present investigation was carried out to analyse, immunohistochemically, in vivo leptin expression in cartilage and bone cells, the latter restricted to the elements of the osteogenic system (stromal cells, osteoblasts, osteocytes, bone lining cells). Observations were performed on the first lumbar vertebra, tibia and femur of four rats and on the humerus, femur and acromion of four patients. Histological sections of paraffin-embedded bone samples were immunostained using antibody to leptin. The results showed that, in growing rat bone, leptin is expressed in chondrocytes and stromal cells, but not in osteoblasts; bone lining cells were not found in the microscopic fields examined. In adult human bone, leptin is expressed in chondrocytes, stromal cells and bone lining cells; osteoblasts were not found in the microscopic fields examined. Osteocytes were found to be leptin positive only occasionally and focally in both rat and human bone. The in vivo findings reported show, for the first time, that leptin appears to be expressed only in the cells of the osteogenic lineage (stromal cells, bone lining cells, osteocytes) that, with respect to osteoblasts, are permanent and inactive, i.e. in those cells that according to our terminology constitute the bone basic cellular system (BBCS). Because the BBCS seems to be primarily involved in sensing and integrating mechanical strains and biochemical factors and then in triggering and driving bone formation and/or bone resorption, it appears that leptin seems to be mainly involved in modulating the initial phases of bone modelling and remodelling processes.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo leptin expression in cartilage and bone cells of growing rats and adult humans

et al. 2004

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“…Recently, leptin was described as a new regulator of bone growth, acting either through a neuronal network to release an unidentified antiosteogenic factor (20,21) or directly by inducing osteoblast proliferation, collagen synthesis, and bone mineralization (22,23). Leptin is also a skeletal growth factor that stimulates endochondral ossification (24). Because functional leptin receptor has been shown to be expressed in normal human cartilage (25), it can be speculated that leptin could also act on this articular connective tissue, especially during osteoarthritis (OA), a disease in which great metabolic changes of chondrocytes are observed.…”

Section: Conclusion These Findings Suggest a New Peripheral Functionmentioning

confidence: 99%

Evidence for a key role of leptin in osteoarthritis

Dumond¹,

Presle²,

Terlain³

et al. 2003

Arthritis & Rheumatism

495

416

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Objective. To evaluate the contribution of leptin (an adipose tissue-derived hormone) to the pathophysiology of osteoarthritis (OA), by determining the level of leptin in both synovial fluid (SF) and cartilage specimens obtained from human joints. We also investigated the effect of leptin on cartilage, using intraarticular injections of leptin in rats.Methods. Leptin levels in SF samples obtained from OA patients undergoing either knee replacement surgery or knee arthroscopy were measured by enzymelinked immunosorbent assay. In addition, histologic sections of articular cartilage and osteophytes obtained during surgery for total knee replacement were graded using the Mankin score, and were immunostained using antibodies to leptin, transforming growth factor ␤ (TGF␤), and insulin-like growth factor 1 (IGF-1). For experimental studies, various doses of leptin (10, 30, 100, and 300 g) were injected into the knee joints of rats. Tibial plateaus were collected and processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (ObRb), and growth factors by reverse transcriptasepolymerase chain reaction and immunohistochemical analysis.Results. Leptin was observed in SF obtained from human OA-affected joints, and leptin concentrations correlated with the body mass index. Marked expression of the protein was observed in OA cartilage and in osteophytes, while in normal cartilage, few chondrocytes produced leptin. Furthermore, the pattern and level of leptin expression were related to the grade of cartilage destruction and paralleled those of growth factors (IGF-1 and TGF␤1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes and induced the synthesis of IGF-1 and TGF␤1 in cartilage at both the messenger RNA and the protein levels.Conclusion. These findings suggest a new peripheral function of leptin as a key regulator of chondrocyte metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.

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“…Although an effect of leptin on bone formation has also been reported, its effects on bone metabolism remain controversial. Some studies have reported that it has anabolic effects on bone [16][17][18][19][20][21][22][23][24], while other studies reported suppressive effects on bone formation [25,26].…”

Section: Introductionmentioning

confidence: 99%

Possible Involvement of Leptin in the Elevated Osteoblastic Activity Observed in High Turnover Type Osteoporosis of Ovariectomized Mice

Tezuka¹

2014

J Autacoids

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Postmenopausal osteoporosis is a high turnover type of osteoporosis induced by estrogen deficiency following menopause. In this type of osteoporosis, the osteoblastic activity is known to be elevated even though bone resorption by osteoclasts eventually exceeds bone formation by osteoblasts, resulting in the deterioration of the bone structure. Although the mechanisms underlying the progression of bone resorption in this disease are relatively well understood, the mechanisms underlying the elevated osteoblastic activity are yet to be elucidated. The purpose of this study is to investigate the possibility that leptin, a 16 kDa circulating hormone secreted mainly by white adipose tissue, is involved in the development and/or progression of the high turnover type of osteoporosis. Immunohistochemical analysis and ELISA were used to examine the expression of leptin in bones of ovariectomized mice. To investigate the effect of leptin on proliferation and osteoblastic differentiation of bone marrow stromal cells, cell proliferation assay and real-time RT-PCR analysis were performed using a mouse bone marrow stromal cell line, MMSC3. Immunohistochemistry and ELISA revealed enhanced expression of leptin in bone marrows of ovariectomized mice. A cell proliferation assay detected no significant effect of leptin on the proliferation of MMSC3 cells. In contrast, real-time RT-PCR revealed that leptin promoted the osteoblastic differentiation of this cell line. Estrogen depletion caused by ovariectomy induces the upregulation of leptin expression in the bone marrow cavity, which leads to the elevated osteoblastic activity observed in the early phase of high turnover type osteoporosis of ovariectomized mice.

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Potential Role of Leptin in Endochondral Ossification

Cited by 118 publications

References 41 publications

In vivo leptin expression in cartilage and bone cells of growing rats and adult humans

In vivo leptin expression in cartilage and bone cells of growing rats and adult humans

Evidence for a key role of leptin in osteoarthritis

Possible Involvement of Leptin in the Elevated Osteoblastic Activity Observed in High Turnover Type Osteoporosis of Ovariectomized Mice

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