Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice

Oestreich, Arin K.; Carleton, Stephanie M.; Yao, Xiaomei; Gentry, Bettina A.; Raw, C. E.; Brown, Marybeth; Pfeiffer, Ferris M.; Wang, Yong; Phillips, Charlotte L.

doi:10.1007/s00198-015-3226-7

Cited by 29 publications

(22 citation statements)

References 48 publications

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“…We do not know whether the observed increases in BMC and BMD represent a direct effect of the ActRIIB.Fc on the bone or an indirect effect resulting from increased muscle mass. Positive correlation between muscle mass and bone mass has been reported with partial or complete myostatin inactivation in mice [50,51,53,54]. Recent studies suggest that myostatin may have direct catabolic effects on bone metabolism [55–58].…”

Section: Discussionmentioning

confidence: 99%

Administration of an activin receptor IIB ligand trap protects male juvenile rhesus macaques from simian immunodeficiency virus-associated bone loss

Guo

Pencina

O'Connell

et al. 2017

Bone

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HIV-infected individuals are at an increased risk of osteoporosis despite effective viral suppression. Observations that myostatin null mice have increased bone mass led us to hypothesize that simian immunodeficiency virus (SIV)-associated bone loss may be attenuated by blocking myostatin/TGFβ signaling. In this proof-of-concept study, pair-housed juvenile male rhesus macaques were inoculated with SIVmac239. Four weeks later, animals were treated with vehicle or Fc-conjugated soluble activin receptor IIB (ActR2B·Fc, iv. 10 mg ∗ kg−1 ∗ week−1) – an antagonist of myostatin and related members of TGFβ superfamily. Limb and trunk bone mineral content (BMC) and density (BMD) using dual-energy X-Ray absorptiometry, circulating markers of bone growth and turnover, and serum testosterone levels were measured at baseline and during the 12-week intervention period. The increase in BMC was significantly greater in the ActRIIB.Fc-treated group (+8 g) than in the placebo group (−4 g) (p < 0.05). BMD also increased significantly more in the ActRIIB.Fc-treated macaques (+0.03 g/cm2) than in the placebo-treated animals (+0 g/cm2) (p < 0.005). Serum osteocalcin was about two-fold higher in the ActRIIB.Fc-treated group than in the placebo group (p < 0.05), but serum C-terminal telopeptide and testosterone levels did not differ significantly between groups. The expression levels of TNFalpha (p < 0.05), GADD45 (p

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Section: Discussionmentioning
confidence: 99%

Administration of an activin receptor IIB ligand trap protects male juvenile rhesus macaques from simian immunodeficiency virus-associated bone loss
Guo
¹
,
Pencina
²
,
O'Connell
³

et al. 2017
Bone
6
3
4
0
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“…Hamrick revealed that GDF8 deficiency had load‐dependent effects on the increased osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) in mice . Another study confirmed that the lack of GDF8 improved the reduced femoral bone biomechanical strength of osteogenesis imperfecta model mice partially . In addition, GDF8 regulates osteoclast differentiation directly and its inhibition reduced bone erosion in arthritis model mice .…”

Section: Introductionmentioning
confidence: 94%

“…9 Another study confirmed that the lack of GDF8 improved the reduced femoral bone biomechanical strength of osteogenesis imperfecta model mice partially. 10 In addition, GDF8 regulates osteoclast differentiation directly and its inhibition reduced bone erosion in arthritis model mice. 11 However, the functions of GDF8 in bone formation and bone resorption require further investigation.…”

Section: Introductionmentioning
confidence: 99%

GDF8 inhibits bone formation and promotes bone resorption in mice
Chen
¹
,
Guo
²
,
Guo
³

et al. 2017
Clin Exp Pharma Physio
25
1
24
0
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Growth Differentiation Factor 8 (GDF8), also called myostatin, is a member of the transforming growth factor (TGF)-β super-family. As a negative regulator of skeletal muscle growth, GDF8 is also associated with bone metabolism. However, the function of GDF8 in bone metabolism is not fully understood. Our study aimed to investigate the role of GDF8 in bone metabolism, both in vitro and in vivo. Our results showed that GDF8 had a negative regulatory effect on primary mouse osteoblasts, and promoted receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro. Intraperitoneal injection of recombinant GDF8 repressed bone formation and accelerated bone resorption in mice. Furthermore, treatment of aged mice with a GDF8 neutralizing antibody stimulated new bone formation and prevented bone resorption. Thus, our study showed that GDF8 plays a significant regulatory role in bone formation and bone resorption, thus providing a potential therapeutic pathway for osteoporosis.

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“…Myostatin may play a more prominent role in the pathogenesis of disease states that affect bone. Using a mouse model of osteogenesis imperfecta, genetically reduced levels of myostatin improved muscle mass and bone strength . In a mouse model of rheumatoid arthritis, myostatin gene knockout or administration of an inhibitory antibody against myostatin reduced bone erosion .…”

Section: Myostatinmentioning
confidence: 99%

“…Using a mouse model of osteogenesis imperfecta, genetically reduced levels of myostatin improved muscle mass and bone strength . In a mouse model of rheumatoid arthritis, myostatin gene knockout or administration of an inhibitory antibody against myostatin reduced bone erosion . Mice administered RAP‐031, a soluble form of the activin IIB receptor that binds and inactivates myostatin and other activin IIB receptor ligands, had larger pectoralis, rectus femoris, and gastrocnemius muscles, and these alterations were associated with increased trabecular number and bone volume fraction (BV/TV) at the proximal tibia .…”

Section: Myostatinmentioning
confidence: 99%

Muscle–bone interactions: movement in the field of mechano–humoral coupling of muscle and bone
Cardozo
¹
,
Graham
²

2017
Annals of the New York Academy of Sciences
23
0
28
0
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Cyclical, mechanical loading of bone by skeletal muscle is widely recognized as a critical determinant of bone structure and mass. A growing body of evidence indicates that substances released from skeletal muscle into the bloodstream also regulate bone mass and metabolism. In this commentary, we discuss the status of research in the area of humoral regulation of bone mass by the skeletal muscle secretome, with an emphasis on the roles of myostatin, irisin, interleukin-6, and exosomes. The interplay between muscle, bone, and other modulators of bone mass, including circadian rhythm and sympathetic tone, is also discussed.

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Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice

Abstract: Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Cited by 29 publications

References 48 publications

Administration of an activin receptor IIB ligand trap protects male juvenile rhesus macaques from simian immunodeficiency virus-associated bone loss

Administration of an activin receptor IIB ligand trap protects male juvenile rhesus macaques from simian immunodeficiency virus-associated bone loss

GDF8 inhibits bone formation and promotes bone resorption in mice

Muscle–bone interactions: movement in the field of mechano–humoral coupling of muscle and bone

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