The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of replication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent parathyroid hormone (PTH) administration, but the mechanism of this phenomenon has remained unknown. We report that daily PTH injections in mice with either normal bone mass or osteopenia due to defective osteoblastogenesis increased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing their apoptosis — the fate of the majority of these cells under normal conditions. The antiapoptotic effect of PTH was sufficient to account for the increase in bone mass, and was confirmed in vitro using rodent and human osteoblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppression of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.
Robert L. Jilka, Robert S. Weinstein, Teresita Bellido, Paula Roberson, A. Michael Parfitt, Stavros C. Manolagas
Title and authors | Publication | Year |
---|---|---|
Parathyroid hormone regulates fates of osteoblast precursors in vivo
Deepak Balani, Noriaki Ono, Henry M Kronenberg |
Journal of Clinical Investigation | 2017 |
Comparison of the effects of once-weekly and once-daily rhPTH (1-34) injections on promoting fracture healing in rodents: rhPTH (1-34) PROMOTES FRACTURE HEALING
W Zhang, J Zhu, T Ma, C Liu, B Hai, G Du, H Wang, N Li, H Leng, Y Xu, C Song |
Journal of orthopaedic research : official publication of the Orthopaedic Research Society | 2017 |
Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2: MURAMYL DIPEPTIDE IS A NOVEL INDUCER OF BONE FORMATION
OJ Park, J Kim, J Yang, CH Yun, SH Han |
Journal of Bone and Mineral Research | 2017 |
Heterotrimeric G proteins in the control of parathyroid hormone actions
M Bastepe, S Turan, Q He |
Journal of Molecular Endocrinology | 2017 |
Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate
Y Fan, J Hanai, PT Le, R Bi, D Maridas, V DeMambro, CA Figueroa, S Kir, X Zhou, M Mannstadt, R Baron, RT Bronson, MC Horowitz, JY Wu, JP Bilezikian, DW Dempster, CJ Rosen, B Lanske |
Cell Metabolism | 2017 |
Parathyroid Hormone Signaling in Osteocytes: PTH SIGNALING IN OSTEOCYTES
MN Wein |
JBMR Plus | 2017 |
Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders.
Liu J, Khalil RA |
Progress in molecular biology and translational science | 2017 |
Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia.
Chen J, Khalil RA |
Progress in molecular biology and translational science | 2017 |
Wnt Signaling in Kidney Development and Disease
Wang Y, Zhou CJ, Liu Y |
Progress in molecular biology and translational science | 2017 |
Wnt Signaling in Hematological Malignancies.
Grainger S, Traver D, Willert K |
Progress in molecular biology and translational science | 2017 |
Matrix Metalloproteinases in Myocardial Infarction and Heart Failure
DeLeon-Pennell KY, Meschiari CA, Jung M, Lindsey ML |
Progress in molecular biology and translational science | 2017 |
Role of cortical bone in hip fracture
J Reeve |
BoneKEy Reports | 2017 |
Modeling the Effect of Curvature on the Collective Behavior of Cells Growing New Tissue
MA Alias, PR Buenzli |
Biophysical Journal | 2017 |
Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition
A Varela-López, J Ochoa, J Llamas-Elvira, M López-Frías, E Planells, MC Ramirez-Tortosa, C Ramirez-Tortosa, F Giampieri, M Battino, J Quiles |
Nutrients | 2017 |
Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate
R Arai, D Takahashi, M Inoue, T Irie, T Asano, T Konno, MA Terkawi, T Onodera, E Kondo, N Iwasaki |
BMC musculoskeletal disorders | 2017 |
Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model
T Makihara, T Yoshioka, H Sugaya, K Aoto, H Wada, K Uemura, K Tanaka, H Akaogi, M Yamazaki, H Mishima |
Bone Marrow Research | 2017 |
Treatment of postmenopausal osteoporosis: a literature-based algorithm for use in the public health care system
EL Caires, MC Bezerra, AF de Junqueira, SM de Fontenele, SC de Andrade, CB dAlva |
Revista Brasileira de Reumatologia (English Edition) | 2017 |
Bone histomorphometry in de novo renal transplant recipients indicates a further decline in bone resorption 1 year posttransplantation
P Evenepoel, GJ Behets, L Viaene, PC D'Haese |
Kidney International | 2017 |
CCL2/Monocyte Chemoattractant Protein 1 and Parathyroid Hormone Action on Bone
JA Siddiqui, NC Partridge |
Frontiers in Endocrinology | 2017 |
Effect of teriparatide (rh-PTH 1–34) versus bisphosphonate on the healing of osteoporotic vertebral compression fracture: A retrospective comparative study
A Iwata, M Kanayama, F Oha, T Hashimoto, N Iwasaki |
BMC musculoskeletal disorders | 2017 |
Intermittent parathyroid hormone improve bone microarchitecture of the mandible and femoral head in ovariectomized rats
YJ Chen, SP Wang, FC Cheng, PY Hsu, YF Li, J Wu, HL Huang, MT Tsai, JT Hsu |
BMC musculoskeletal disorders | 2017 |
PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization
C Zhou, J Meng, C Zhao, C Ye, H Zhu, B Hu, BC Heng, Y Shen, T Lin, X Yang, Z Shi, W Shen, S Yan, D Miao |
PloS one | 2017 |
Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A Narrative Review: DIFFERENTIAL EFFECTS OF PARATHYROID HORMONE REGIMEN
KM Kim, SY Lee, Y Rhee |
JBMR Plus | 2017 |
Assessment of the effect of systemic delivery of sclerostin antibodies on Wnt signaling in distraction osteogenesis
MM Alzahrani, AM Makhdom, F Rauch, D Lauzier, M Kotsiopriftis, S Ghadakzadeh, RC Hamdy |
Journal of Bone and Mineral Metabolism | 2017 |
Combination of PTH (1-34) with anti-IL17 prevents bone loss by inhibiting IL-17/N-cadherin mediated disruption of PTHR1/LRP-6 interaction
MN Mansoori, P Shukla, D Singh |
Bone | 2017 |
The Role of Bone Remodelling in Maintaining and Restoring Bone Health: an Overview
E Raubenheimer, H Miniggio, L Lemmer, W Heerden |
Clinical Reviews in Bone and Mineral Metabolism | 2017 |
Bone Lining Cells: Normal Physiology and Role in Response to Anabolic Osteoporosis Treatments
MN Wein |
Current Molecular Biology Reports | 2017 |
Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway
SC Tao, T Yuan, BY Rui, ZZ Zhu, SC Guo, CQ Zhang |
Theranostics | 2017 |
Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions
G Tong, Y Meng, S Hao, S Hu, Y He, W Yan, D Yang |
Medical science monitor : international medical journal of experimental and clinical research | 2017 |
Multiscale Mechanobiology of Bone Remodeling and Adaptation
P Pivonka |
Multiscale Mechanobiology of Bone Remodeling and Adaptation | 2017 |
Osteoblast as a target of anti-osteoporotic treatment
A Corrado, ER Sanpaolo, SD Bello, FP Cantatore |
Postgraduate Medicine | 2017 |
Parathyroid Hormone (PTH) Induces Autophagy to Protect Osteocyte Cell Survival from Dexamethasone Damage
L Zhu, J Chen, J Zhang, C Guo, W Fan, Y Wang, Z Yan |
Medical science monitor : international medical journal of experimental and clinical research | 2017 |
The Proteasome and Myeloma-Associated Bone Disease
F Accardi, D Toscani, F Costa, F Aversa, N Giuliani |
Calcified Tissue International | 2017 |
G protein-coupled receptors as anabolic drug targets in osteoporosis
N Diepenhorst, P Rueda, AE Cook, P Pastoureau, M Sabatini, CJ Langmead |
Pharmacology & Therapeutics | 2017 |
Single-dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical-sized calvarial defect: BONE REGENERATION BY OCP/COL WITH TERIPARATIDE SOLUTION
F Kajii, A Iwai, H Tanaka, K Matsui, T Kawai, S Kamakura |
Journal of biomedical materials research. Part B, Applied biomaterials | 2017 |
Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss
Stephen E Harris, Michael Rediske, Rebecca Neitzke, Audrey Rakian |
Cell, stem cells and regenerative medicine | 2017 |
Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions.
Tong G, Meng Y, Hao S, Hu S, He Y, Yan W, Yang D |
Medical science monitor : international medical journal of experimental and clinical research | 2017 |
Parathyroid Hormone (PTH) Induces Autophagy to Protect Osteocyte Cell Survival from Dexamethasone Damage.
Zhu L, Chen J, Zhang J, Guo C, Fan W, Wang YM, Yan Z |
Medical science monitor : international medical journal of experimental and clinical research | 2017 |