ACTH enhances chondrogenesis in multipotential progenitor cells and matrix production in chondrocytes

Evans, Jodi F.; Niu, Qing-Tian; Canas, Jose A; Shen, Chwan-L; Aloia, John F.; Yeh, James K.

doi:10.1016/j.bone.2004.03.015

Cited by 33 publications

(47 citation statements)

References 42 publications

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“…ACTH induces expression of type II and type X collagens in bone marrow-derived stem cells and in costal chondrocytes, which are representative of committed resting chondrocytes in the growth plate. Presumably, ACTH promotes the development of the OA chondrocyte phenotype of progenitor cells and increases matrix production and differentiation of early committed chondrocytes (15). We propose that, accordingly, ␣-MSH stimulates differentiation of chondrocyte progenitors or early differentiated chondrocytes during endochondral ossification, which enhances linear bone growth rather than stabilizing the permanent cartilage phenotype with regard to matrix composition and MMP gene expression profile.…”

Section: Discussionmentioning

confidence: 98%

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The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components

Grässel¹,

Opolka²,

Anders³

et al. 2009

Arthritis & Rheumatism

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Human articular chondrocytes are target cells for alpha-MSH. The effects of alpha-MSH on expression of cytokines and MMPs suggest that this neuropeptide plays a role in inflammatory and degenerative processes in cartilage. It is conceivable that inflammatory reactions can be mitigated by the induction of endogenous MCs or administration of alpha-MSH to the affected joints. The induction pattern of regulatory and structural ECM components such as collagens as well as SOX9 and anabolic and catabolic cytokines points to a function of alpha-MSH as a trophic factor in skeletal development during endochondral ossification rather than as a factor in homeostasis of permanent cartilage.

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Section: Discussionmentioning

confidence: 98%

“…The same authors detected MC-3R expression in these chondrocytes (by definition, described as resting chondrocytes) and in 2 chondrocyte cell lines (15). Recently, an inhibitory effect of ␣-MSH on tumor necrosis factor ␣ (TNF␣)-induced expression of matrix metalloproteinase 13 (MMP-13) was reported.…”

mentioning

confidence: 93%

The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components

Grässel¹,

Opolka²,

Anders³

et al. 2009

Arthritis & Rheumatism

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“…This hormone has a role in modulating the immune system by reducing the production of immunoglobulin by B-lymphocytes [Tsagarakis and Grossman, 1994]. Corticotropin treatment is reported to increase the proliferation of multipotential progenitor populations and also promote the development of a chondrocyte phenotype from multipotential progenitor populations [Evans et al, 2004]. Furthermore, corticotropin is known to stimulate keratinocyte proliferation thus playing a role in wound healing and also to activate the epithelial and mesenchymal cell proliferation and differentiation throughout the parenchyma during pulmonary maturation [Muglia et al, 1999].…”

Section: Discussionmentioning

confidence: 98%

Proteomic profiling of distinct clonal populations of bone marrow mesenchymal stem cells

Mareddy

Broadbent

Crawford

et al. 2009

J of Cellular Biochemistry

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Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing MSC self-renewal and differentiation remain largely unknown. The development of sophisticated techniques, in particular clinical proteomics, has enabled researchers in various fields to identify and characterize cell specific biomarkers for therapeutic purposes. This study seeks to understand the cellular and sub-cellular processes responsible for the existence of stem cell populations in bone marrow samples by revealing the whole cell proteome of the clonal cultures of bone marrow-derived MSCs (BMSCs). Protein profiling of the MSC clonal populations was conducted by Two-Dimensional Liquid Chromatography/Matrix-Assisted Laser Desorption/Ionisation (MALDI) Mass Spectrometry (MS). A total of 83 proteins were identified with high confidence of which 11 showed differential expression between subpopulations, which included cytoskeletal and structural proteins, calcium binding proteins, cytokinetic proteins, and members of the intermediate filament family. This study generated a proteome reference map of BMSCs from the clonal populations, which will be valuable to better understand the underlying mechanism of BMSC self-renewal and differentiation.

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“…ACTH has been reported to be capable of inducing osteoblast proliferation (15,39). In addition, all five melanocortin receptors are expressed on osteoblasts (39).…”

Section: Discussionmentioning

confidence: 99%

“…b ACTH plays a role in ostoblast proliferation (15,39). c Insulin acts on the adipocyte to release leptin (5).…”

Section: Discussionmentioning

confidence: 99%

Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density

Cawley¹,

Yanik²,

Woronowicz³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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YP.Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density. Am J Physiol Endocrinol Metab 299: E189 -E197, 2010. First published May 11, 2010; doi:10.1152/ajpendo.00516.2009.-Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme, and mice bearing CPE mutations exhibit an obese and diabetic phenotype. Studies on CPE knockout (KO) mice revealed poor prohormone processing, resulting in deficiencies in peptide hormones/neuropeptides such as insulin, gonadotropin-releasing hormone, and cocaineand amphetamine-regulated transcript (CART). Here, we show that CPE KO mice, an obese animal model, have low bone mineral density (BMD) accompanied by elevated plasma CTX-1 (carboxy-terminal collagen crosslinks), and osteocalcin, indicators of increased bone turnover. Receptor activator for NF-B ligand (RANKL) expression was elevated ϳ2-fold relative to osteoprotegerin in the femur of KO animals, suggesting increased osteoclastic activity in the KO mice. In the hypothalamus, mature CART, a peptide involved in eating behavior and implicated in bone metabolism, was undetectable. The melanocortin and neuropeptide Y (NPY) systems in the hypothalamus have also been implicated in bone remodeling, since MC4R KO and NPY KO mice have increased BMD. However, reduction of ␣-MSH, the primary ligand of MC4R by up to 94% and the lack of detectable NPY in the hypothalamus of CPE KO do not recapitulate the singlegene KO phenotypes. This study highlights the complex physiological interplay between peptides involved in energy metabolism and bone formation and furthermore suggests the possibility that patients, bearing CPE and CART mutations leading to inactive forms of these molecules, may be at a higher risk of developing osteoporosis. CARBOXYPEPTIDASE E (CPE) is a processing enzyme that is highly expressed in endocrine cells and peptidergic neurons (17,19). It functions to cleave carboxy-terminally extended lysine and arginine residues from peptide hormone and neuropeptide intermediates to form bioactive peptides in the regulated secretory pathway (RSP). In addition to its enzymatic function, CPE has been shown to facilitate trafficking of several prohormones into the granules of the RSP (10, 26). Recently, live-cell imaging and coimmunoprecipitation studies demonstrated a role for its cytoplasmic carboxyl terminus in the transport of peptidergic vesicles via interaction with dynactin, an anterograde microtubule-based motor protein complex (27,28). The involvement of CPE in multiple cellular functions would suggest that deficiencies in CPE would lead to many pathologies. Indeed, the CPE knockout (KO) mouse exhibits multiple endocrinopathies leading to diabetes, infertility, and obesity (7).During our initial characterization of the phenotype of the CPE KO mice, which included physical and biochemical measurements as well as behavioral tests (7), we observed unexpectedly that bone mineral density (BMD) measurements of the CPE KO mice were lower th...

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ACTH enhances chondrogenesis in multipotential progenitor cells and matrix production in chondrocytes

Cited by 33 publications

References 42 publications

The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components

The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components

Proteomic profiling of distinct clonal populations of bone marrow mesenchymal stem cells

Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density

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