scholarly journals Increased Potential of Bone Formation With Intravenous Injection of Parathyroid Hormone-minicircle DNA Vector 

2020 ◽  
Author(s):  
Jang-Woon Kim ◽  
Narae Park ◽  
Jaewoo Kang ◽  
Yena Kim ◽  
Hyerin Jung ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Bone Structure ◽  
Therapeutic Potential ◽  
Treatment Of Osteoporosis ◽  
Intravenous Injections ◽  
Parathyroid Hormone Related Protein ◽  
Dna Vectors ◽  
Minicircle Dna

Abstract Background: Osteoporosis is usually treated with long-term usage of anti-osteoporotic agents. However, poor drug compliance and emerging side effects sometimes are limitations for the treatment of osteoporosis. Parathyroid hormone-related protein (PTHrP) is needed for normal bone formation and remodeling. We attempted a new method using minicircle vectors (mc) encoding PTHrP analogs. Methods: We generated mc encoding the infusion of PTHrP 1-34 with 107-139 (mc 1-34+107-139). Ovariectomized (OVX) model was induced in 12-week-old C57BL/6 female mice. mc 1-34+107-139 was administered three times weekly via intravenous injections. Results: mc 1-34+107-139 significantly increased bone formation compared with the OVX group and decreased the bone resorption. PTHrP mc DNA vector was effective in increasing the quality of trabecular bone structure. Conclusions: These results provide experimental evidence for the therapeutic potential of minicircle DNA vectors in OVX model. This study is a first attempted proof-of-concept gene therapy using minicircle vectors for the treatment of osteoporosis.

scholarly journals Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector

2021 ◽  
Vol 22 (16) ◽  
pp. 9069
Author(s):  
Jang-Woon Kim ◽  
Narae Park ◽  
Jaewoo Kang ◽  
Yena Kim ◽  
Hyerin Jung ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Bone Structure ◽  
Human Mesenchymal Stem Cells ◽  
Treated Group ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Alternative Delivery ◽  
Minicircle Dna

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1–34 and 107–139); mcPTHrP 1–34+107–139 using a minicircle vector. We also transfected mcPTHrP 1–34+107–139 into human mesenchymal stem cells (MSCs) and generated Thru 1–34+107–139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1–34+107–139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1–34+107–139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1–34+107–139 using the minicircle technology for the treatment of osteoporosis.

scholarly journals Malignant Myeloma in a Patient after Treatment for Osteoporosis with Teriparatide; a Rare Coincidence

2008 ◽  
Vol 1 ◽  
pp. CCRep.S1026 ◽  
Author(s):  
Terje Forslund ◽  
Anna-Mari Koski ◽  
Arvo Koistinen ◽  
Anu Sikiö
Keyword(s):  
Parathyroid Hormone ◽  
Theoretical Basis ◽  
Bone Structure ◽  
Exclusion Criterion ◽  
Human Parathyroid Hormone ◽  
Treatment Of Osteoporosis ◽  
Teriparatide Treatment ◽  
Direct Association ◽  
Metastasis Development ◽  
Structure Regulation

A breakthrough in understanding of mechanisms of bone structure regulation has brought about the introduction of the new synthetic recombinant human parathyroid hormone 1–34 (PTH1-34; Teriparatide) in the treatment of osteoporosis. These mechanisms, involving the RANKL, RANK, and osteoprotegerin system, are also known to be involved in malignant myeloma (MM) and tumor and bone metastasis development. We report a case in which MM was found after treatment of osteoporosis with teriparatide. We were unable to demonstrate any direct association between the MM and teriparatide treatment. However, it seemed intriguing that similar mechanisms are activated in the development of MM as those being working during teriparatide treatment. In the view of our case, we propose that MM by examination of serum protein fraction should be searched for prior to treatment with teriparatide as it is an exclusion criterion in teriparatide treatment of secondary osteoporosis. A search for other metastatic diseases prior to teriparatide treatment should eventually also be considered. The theoretical basis for our proposal is discussed.

scholarly journals Bone Health in Patients with Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Vit Zikan
Keyword(s):  
Multiple Sclerosis ◽  
Bone Formation ◽  
Bone Structure ◽  
Bone Fractures ◽  
Osteoporotic Fractures ◽  
Mechanical Stimuli ◽  
Osteocyte Apoptosis ◽  
Motor Disability ◽  
Risk Of Falls

Multiple sclerosis (MS) is a gait disorder characterized by acute episodes of neurological defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids (GCs) treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immobilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. There are currently no recommendations how to best prevent and treat osteoporosis in patients with MS. However, devastating effect of immobilization on the skeleton in patients with MS underscores the importance of adequate mechanical stimuli for maintaining the bone structure and its mechanical competence. The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, will be promising for prevention and treatment of osteoporosis in patients with MS.

scholarly journals Role of Biomolecules in Osteoclasts and Their Therapeutic Potential for Osteoporosis

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 747
Author(s):  
Xin Zhao ◽  
Suryaji Patil ◽  
Fang Xu ◽  
Xiao Lin ◽  
Airong Qian
Keyword(s):  
Transcription Factors ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Metabolism ◽  
Therapeutic Potential ◽  
Bone Microarchitecture ◽  
Treatment Of Osteoporosis ◽  
Non Coding Rnas ◽  
And Function

Osteoclasts (OCs) are important cells that are involved in the regulation of bone metabolism and are mainly responsible for coordinating bone resorption with bone formation to regulate bone remodeling. The imbalance between bone resorption and formation significantly affects bone metabolism. When the activity of osteoclasts exceeds the osteoblasts, it results in a condition called osteoporosis, which is characterized by reduced bone microarchitecture, decreased bone mass, and increased occurrences of fracture. Molecules, including transcription factors, proteins, hormones, nucleic acids, such as non-coding RNAs, play an important role in osteoclast proliferation, differentiation, and function. In this review, we have highlighted the role of these molecules in osteoclasts regulation and osteoporosis. The developed therapeutics targeting these molecules for the treatment of osteoporosis in recent years have also been discussed with challenges faced in clinical application.

Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity

1993 ◽  
Vol 39 (6) ◽  
pp. 695-698 ◽  
Author(s):  
Mark W. Savage ◽  
William D. Fraser ◽  
Charles W. Bodmer ◽  
Andrew F. Ginty ◽  
James A. Gallagher ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Circulating Levels ◽  
Tumour Activity
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