Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

Kawano, Masatoshi; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

doi:10.1016/j.bbrc.2011.01.071

Cited by 77 publications

(64 citation statements)

References 44 publications

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“…In fact, as reported in the literature, it can improve angiogenesis, fibroblast and osteoblast proliferation, collagen biosynthesis, and production of growth factors, as evidenced by MTT test and alkaline phosphatase histochemical staining [36, 37]. In vivo and in vitro studies suggested that hyaluronic acid plays important roles in bone wound healing by enhancement of osteoblast differentiation through the downregulation of BMP-2 antagonists [38, 39], whereas lysine and proline are important metabolic factors regulating collagen matrix synthesis during osteogenesis [40]. …”

Section: Resultsmentioning

confidence: 98%

New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

Franco

Miccoli

Limongelli

et al. 2014

International Journal of Dentistry

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Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the most serious side effect in patients receiving bisphosphonates (BPs) for neoplastic disease and osteoporosis. The aim of this study is to propose a new dimensional stage classification, guiding the surgical treatment of BRONJ patients, and to evaluate the success rate of this new management. From 2004 to 2013, 203 neoplastic and osteoporotic patients with 266 BRONJ lesions were referred to the Odontostomatology Unit of the University of Bari. All patients underwent surgery after suspension of BPs therapy and antibiotic treatment. The surgical procedure was complemented by piezosurgery and followed by the application of hyaluronate and amino acids. The new dimensional staging suggests the choice of the surgical approach, and allows the prediction of postoperative complications and soft and hard tissues healing time, guiding the surgical treatment protocol. This protocol could be a successful management strategy for BRONJ, considering the low recurrences rate and the good stabilisation of the surgical sites observed after a long-term follow-up.

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Section: Resultsmentioning

confidence: 98%

New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

Franco

Miccoli

Limongelli

et al. 2014

International Journal of Dentistry

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“…The cells were kept in a water-jacketed cell incubator at 37°C under 5% CO 2 in air. The MG63 cells express markers for osteogenic differentiation such as alkaline phosphatase enzyme activity and form mineralized nodules showing that they are representative for native osteoblasts [27,28]. The cells were trypsinized (0.25% trypsin/EDTA) and reseeded upon reaching confluence.…”

Section: Methodsmentioning

confidence: 99%

The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca<sup>2+</sup> Handling and Induces Ca<sup>2+</sup>-Independent Apoptosis

et al. 2013

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The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC₅₀ value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca²⁺ concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca²⁺ also in the presence of the respective L- and T-type voltage-sensitive Ca²⁺ channel blockers nifedipine and NiCl₂. LL-37 had no effect on Ca²⁺ in cells incubated with Ca²⁺-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca²⁺ in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca²⁺ inflow via a mechanism independent of voltage-sensitive Ca²⁺ channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca²⁺.

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“…Previous studies have shown that ALP is a marker for early differentiation of the osteoblast [15,17] while OCN, produced by osteoblasts exclusively, indicates late differentiation and maturity [20]. Further investigation revealed that reduction of hRpn13 expression could markedly promote osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 89%

“…Accordingly, the altered balance between OPG and RANKL activity has been shown to play pivotal roles in the development of osteoporosis in animals and man [2]. Proliferating cell nuclear antigen (PCNA) is a vital proliferation-related protein [3], and alkaline phosphatase (ALP) activity and osteocalcin (OCN) are important indices for the level of differentiation in osteoblasts [15,17,20].…”

Section: Introductionmentioning

confidence: 99%

hRpn13, a newly identified component of the 19S particle, regulates proliferation, differentiation, and function in the human osteoblast-like cell line MG63

et al. 2011

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The 26S proteasome is a key component of the ubiquitin-proteasome system, a process responsible for the majority of cellular protein degradation. The function of the proteasomal ubiquitin receptor hRpn13, a component of the 26S proteasome, is not completely understood. To investigate the role of hRpn13 in the ubiquitin-proteasome system in osteoblasts, the effects of suppressing and overexpressing the hRpn13 gene on proliferation, differentiation, and function of human osteoblast-like MG63 cells were examined. After knockdown of hRpn13 by small interfering RNA, changes in osteoblast proliferation were evaluated by methylthiazolyl-tetrazolium assay. There was an increase in markers for osteoblast proliferation, specifically alkaline phosphatase activity, and elevated protein levels of osteocalcin, proliferating cell nuclear antigen (PCNA), and ubiquitin. Furthermore, hRpn13 knockdown also resulted in a decrease in the ratio between the gene expressions of RANKL and OPG, key players in the pathogenesis of bone diseases that influence the normal balance between bone formation and resorption. In contrast, overexpression of hRpn13 inhibited the proliferation of MG63 cells, and decreased alkaline phosphatase activity as well as protein levels of osteocalcin, PCNA, and ubiquitin while the ratio of RANKL to OPG expression increased. To confirm the function of hRpn13 in the ubiquitin-proteasome pathway, osteoblast proliferation enhancement and ubiquitin accumulation after hRpn2 knockdown was assessed. The results suggest that overexpression of hRpn13 negatively influences proliferation and osteogenic differentiation in MG63 cells. The evidence implies that hRpn13 modulates the influence of osteoblasts on osteoclasts by controlling the stability of regulatory proteins in osteoblasts. In summary, overexpression of hRpn13 promoted the activity of the ubiquitin-proteasome system.

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Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

Cited by 77 publications

References 44 publications

New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

New Dimensional Staging of Bisphosphonate-Related Osteonecrosis of the Jaw Allowing a Guided Surgical Treatment Protocol: Long-Term Follow-Up of 266 Lesions in Neoplastic and Osteoporotic Patients from the University of Bari

The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca<sup>2+</sup> Handling and Induces Ca<sup>2+</sup>-Independent Apoptosis

hRpn13, a newly identified component of the 19S particle, regulates proliferation, differentiation, and function in the human osteoblast-like cell line MG63

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