Hydroxy apatite microspheres enhance gap junctional intercellular communication of human osteoblasts composed of connexin 43 and 45

Nakaoka, Ryusuke; Ahmed, Saifuddin; Tsuchiya, Toshie

doi:10.1002/jbm.a.30328

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…A higher cell density should increase cell-cell interactions (increased cell clustering). Because the establishment of connexin-mediated intercellular gap junctions has been shown to enhance osteoblast differentiation [27][28][29], the apoptosissuppressing effect of HAP could have contributed to the enhanced osteoblastic differentiation on PLLA/HAP composite scaffolds in long-term cultures [11] via the increased number of gap junctions.…”

Section: Discussionmentioning

confidence: 99%

Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds

et al. 2007

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Bone tissue engineering is a promising alternative to bone grafting. Scaffolds play a critical role in tissue engineering. Composite scaffolds made of biodegradable polymers and bone mineral-like inorganic compounds have been reported to be advantageous over plain polymer scaffolds by our group and others. In this study, we compared cellular and molecular events during the early periods of osteoblastic cell culture on poly(l-lactic acid)/hydroxyapatite (PLLA/HAP) composite scaffolds with those on plain PLLA scaffolds, and showed that PLLA/HAP scaffolds improved cell survival over plain PLLA scaffolds. Most cells (MC3T3-E1) on PLLA/HAP scaffolds survived the early culture. In contrast, about 50% of the cells initially adhered to the plain PLLA scaffolds were detached within the first 12 h and showed characteristics of apoptotic cell death, which was confirmed by TUNEL staining and caspase-3 activation. To investigate the mechanisms, we examined the adsorption of serum protein and adhesion molecules to the scaffolds. The PLLA/HAP scaffold adsorbed more than 1.4 times of total serum protein and much greater amounts of serum fibronectin and vitronectin than pure PLLA scaffolds. Similarly, significantly larger amounts of individual adhesion proteins and peptides (fibronectin, vitronectin, RGD, and KRSR) were adsorbed on the PLLA/HAP scaffolds than on the PLLA scaffolds, which resulted in higher cell density on the PLLA/ HAP scaffolds. Furthermore, β1 and β3 integrins and phosphorylation of Fak and Akt proteins in the cells on the PLLA/HAP scaffolds were significantly more abundent than those on PLLA scaffolds, which suggest that enhanced adsorption of serum adhesion proteins to PLLA/HAP scaffolds protect the cells from apoptosis possibly through the integrin-Fak-Akt pathway. These results demonstrate that biomimetic composite scaffolds are advantageous for bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds

et al. 2007

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Development of Cell/Tissue-Based Medical Products

Tsuchiya

2007

YAKUGAKU ZASSHI

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Biodegradable polymers are often used as scaŠolds for tissue engineering and these polymers are in class IV under the revised Pharmaceutical AŠairs Law. From the point of view of safety and e‹cacy, recent problems in the development of tissue-engineered products using biodegradable polymers are summarized in this report.Key words-regenerative medicine; cell/tissue-engineered medical products; biodegradable materials; safety; e‹cacy; scaŠolds

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Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

Jiang¹,

2007

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Gap junctions formed by connexins (Cx) play an important role in transmitting signals between bone cells such as osteoblasts and osteoclasts, cells responsible for bone formation and bone remodeling, respectively. Gap junction intercellular communication (GJIC) has been demonstrated to mediate the process of osteoblast differentiation and bone formation. Furthermore, GJIC propagates Ca 2+ signaling, conveys anabolic effects of hormones and growth factors, and regulates gene transcription of osteoblast differentiation markers. GJIC is also implicated to regulate osteoclast formation, survival and apoptosis. Compared with other bone cells, the most abundant type are osteocytes, which express large amounts of connexins. Mechanosensing osteocytes connect and form gap junctions with themselves and other cells only through the tips of their dendritic processes, a relatively small percent of the total cell surface area compared to other cells. Recent studies show that in addition to gap junctions, osteoblasts and osteocytes express functional hemichannels, the un-opposed halves of gap junction channels. Hemichannels are localized at the cell surface and function independently of gap junctions. Hemichannels in osteocytes mediate the immediate release of prostaglandins in response to mechanical stress. The major challenges remaining in the field are how the functions of these two types of channels are coordinated in bone cells and what the asserted, distinct effects of these channels are on bone formation and remodeling processes, and on conveying signals elicited by mechanical loading. KeywordsBone; Gap Junctions; Hemichannels; Cx43; Connexin; Osteoblast; Osteocyte; Mechanical Stress; Review INTRODUCTION Gap Junctions in Bone CellsGap junctions are transmembrane channels, which connect the cytoplasm of adjacent cells. These channels permit molecules with molecular weights approximately less than 1 kD a such as small metabolites, ions, and intracellular signaling molecules (i.e. calcium, cAMP, inositol triphosphate) to pass through. Gap junction channels have been demonstrated to be important in modulating cell signaling and tissue function in many organs, such as heart, liver, peripheral nerve, ovary, ear and lens of the eye (1-8). Gap junctions are formed by members of a family of sequentially and structurally related proteins known as connexins. Approximately twenty connexins have been identified and cloned from various tissues and cells (9-11). Six monomers of connexins are joined head-to-head across the extracellular "gap" between two adjacent cells (21,26,27). However, we found that Cx45 protein is expressed in bone marrow, but not in osteoblasts, osteocytes and osteoclasts in the alveolar bone tissues of the tooth (28).Functional gap junctions in osteoblasts were first demonstrated with electrical conductance and dye injection (29). Voltage-sensitive gap junction currents were detected in osteoblastic cells derived from calvarias of new-born rats with a single gap junction channel conductance of approxim...

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Hydroxy apatite microspheres enhance gap junctional intercellular communication of human osteoblasts composed of connexin 43 and 45

Cited by 3 publications

References 32 publications

Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds

Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds

Development of Cell/Tissue-Based Medical Products

Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

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