shaly
Iron
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What is Propranolol
Propranolol is a beta-blocker — a type of medication that works by blocking the effects of adrenaline [epinephrine] on beta receptors in the body. This slows the heart rate, reduces blood pressure, and decreases the heart’s workload.
It is commonly prescribed to lower blood presure and many use it for social anxiety.
But research says it could stimulate bone growth.
"normal subjects the intravenous infusion of propranolol caused a significant rise in plasma human growth hormone (HGH) levels" is a conclusion from an articel from "www.sciencedirect.com"
Effects on local igf-1 levels:
In osteogenic systems (MSCs, osteoblasts):
Propranolol increases local IGF-1 expression, alongside BMP-2, Runx2, and ALP.
BMP-2 and IGF-1 act synergistically to promote osteoblast differentiation and mineralization.
The upregulation appears to be via β₂-AR/PKA/CREB inhibition, releasing transcriptional brakes on both BMP-2 and IGF-1 promoters.
→ So in bone tissue, propranolol consistently increases IGF-1 expression.
Effects on bmp-2 expression:
Most evidence is preclinical (rodents, rabbits, and cell culture). Human clinical evidence directly showing BMP-2 upregulation by propranolol is sparse/limited. Clinical translation (dosing, safety, long-term effects) needs more work.
Preclinical studies show thay propranolol (a non-selective β-blocker) significantly increases BMP-2 expression (mRNA and protein) and improves markers of osteogenesis — the magnitude varies by model, but effects are statistically significant in multiple papers (in vitro and in vivo). Below I summarize the best evidence and give the specific studies.
What the evidence shows (summary)
In vivo (rats/rabbits) — systemic propranolol increased bone formation and implant osseointegration and was associated with higher BMP-2 expression in peri-implant/tissue samples. For example, in one rat implant study propranolol raised bone-implant contact from ~42.5% to ~65.0%.
In vitro (osteoblasts / MSCs) — propranolol treatment raised BMP-2 mRNA and protein (and downstream osteogenic markers Runx2, COL-1, OCN), increased ALP activity and calcium deposition (alizarin red), with statistically significant differences vs controls (p<0.05 / p<0.01 in the papers).
Mechanism (proposed) — blockade of β-adrenergic signaling (β2-AR) reduces sympathetic/cAMP/PKA signalling in bone cells, which disinhibits osteogenic programs and is associated with upregulation of BMP-2 and Runx2 — reviews and experimental work describe this pathway.
Studies:
1. Wu Y et al., Int J Mol Med 2021 — Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration.
In rabbits and in cultured MSCs/osteoblasts: propranolol increased BMP-2 (mRNA & protein), Runx2, COL-1, OCN; higher ALP and calcium deposition; statistically significant effects (figures show p<0.05/p<0.01).
2. Al-Subaie AE et al., J Clin Periodontol 2016 — Propranolol enhances bone healing and implant osseointegration in rat tibiae.
In rats treated with propranolol (5 mg/kg): bone-implant contact increased from 42.5 ± 8.8% to 65.0 ± 13.1% (reported in the paper) and histology showed more new bone.
3. Tavakoli M et al., J Oral Maxillofac Res / PMC 2022 — Evaluating systemic administration effect of propranolol on bone-implant contact.
Osteoblasts and osteocytes express β₂-adrenergic receptors (β₂-ARs).
When activated by norepinephrine (NE) from sympathetic nerves:
1. β₂-AR → Gs protein → ↑ cAMP → activates PKA (protein kinase A).
2. PKA phosphorylates CREB and other transcription factors that suppress osteoblast differentiation and promote osteoclast activity.
3. Net result → bone resorption ↑, bone formation ↓.
Propranolol = non-selective β-blocker → inhibits this pathway.
---
2. Mechanistic sequence leading to BMP-2 increase
Step 1. β-blockade reduces cAMP/PKA signaling
Propranolol binds to β₁/β₂-ARs → prevents NE binding.
Intracellular cAMP levels fall → PKA activity decreases.
This changes transcriptional regulation in osteoblast lineage cells.
Evidence: Wu et al. (2021, Int J Mol Med) showed propranolol lowered cAMP and PKA levels in MSCs, correlating with BMP-2 and Runx2 upregulation.
These are the mechanisms behind this:
Relief of inhibitory CREB signaling and activation of osteogenic genes
Under high PKA/CREB signaling, osteogenesis-related genes (including BMP-2, Runx2) are repressed.
β-blockade reduces CREB phosphorylation → de-repression of BMP-2 transcription.
Mechanistic markers in papers: ↓ p-CREB, ↑ BMP-2 mRNA, ↑ Runx2 mRNA, ↑ ALP activity.
---
BMP-2 autocrine/paracrine loop triggers osteogenic differentiation
Once expressed, BMP-2 binds to BMP receptors (BMPR-I/II) on osteoblast precursors:
1. Activates SMAD1/5/8 phosphorylation.
2. SMAD complex with SMAD4 → translocates to nucleus.
3. Induces Runx2, Osterix, COL-1, OCN, ALP, etc.
→ drives osteoblast differentiation and matrix mineralization.
Supporting data: Propranolol-treated MSCs show ↑ p-SMAD1/5/8, ↑ Runx2, ↑ COL-1, ↑ OCN, and stronger Alizarin Red calcium staining.
---
Step 4. Secondary systemic mechanisms
(a) Reduced sympathetic tone → lower RANKL expression in osteoblasts)
Less RANKL → ↓ osteoclastogenesis → bone resorption suppressed.
Allows net anabolic balance favoring BMP-2-driven formation.
(b) Increased local perfusion / angiogenic coupling
Some studies note propranolol modulates VEGF and HIF-1α → indirectly enhances the bone-formation microenvironment.
Its effect on testosterone isn't something massive you might see a neutral or slight drop in testosterone but the effects are minimal and shouldn't be something to be worried about.
Propranolol is a beta-blocker — a type of medication that works by blocking the effects of adrenaline [epinephrine] on beta receptors in the body. This slows the heart rate, reduces blood pressure, and decreases the heart’s workload.
It is commonly prescribed to lower blood presure and many use it for social anxiety.
But research says it could stimulate bone growth.
"normal subjects the intravenous infusion of propranolol caused a significant rise in plasma human growth hormone (HGH) levels" is a conclusion from an articel from "www.sciencedirect.com"
Effects on local igf-1 levels:
In osteogenic systems (MSCs, osteoblasts):
Propranolol increases local IGF-1 expression, alongside BMP-2, Runx2, and ALP.
BMP-2 and IGF-1 act synergistically to promote osteoblast differentiation and mineralization.
The upregulation appears to be via β₂-AR/PKA/CREB inhibition, releasing transcriptional brakes on both BMP-2 and IGF-1 promoters.
→ So in bone tissue, propranolol consistently increases IGF-1 expression.
Effects on bmp-2 expression:
Most evidence is preclinical (rodents, rabbits, and cell culture). Human clinical evidence directly showing BMP-2 upregulation by propranolol is sparse/limited. Clinical translation (dosing, safety, long-term effects) needs more work.
Preclinical studies show thay propranolol (a non-selective β-blocker) significantly increases BMP-2 expression (mRNA and protein) and improves markers of osteogenesis — the magnitude varies by model, but effects are statistically significant in multiple papers (in vitro and in vivo). Below I summarize the best evidence and give the specific studies.
What the evidence shows (summary)
In vivo (rats/rabbits) — systemic propranolol increased bone formation and implant osseointegration and was associated with higher BMP-2 expression in peri-implant/tissue samples. For example, in one rat implant study propranolol raised bone-implant contact from ~42.5% to ~65.0%.
In vitro (osteoblasts / MSCs) — propranolol treatment raised BMP-2 mRNA and protein (and downstream osteogenic markers Runx2, COL-1, OCN), increased ALP activity and calcium deposition (alizarin red), with statistically significant differences vs controls (p<0.05 / p<0.01 in the papers).
Mechanism (proposed) — blockade of β-adrenergic signaling (β2-AR) reduces sympathetic/cAMP/PKA signalling in bone cells, which disinhibits osteogenic programs and is associated with upregulation of BMP-2 and Runx2 — reviews and experimental work describe this pathway.
Studies:
1. Wu Y et al., Int J Mol Med 2021 — Effect and mechanism of propranolol on promoting osteogenic differentiation and early implant osseointegration.
In rabbits and in cultured MSCs/osteoblasts: propranolol increased BMP-2 (mRNA & protein), Runx2, COL-1, OCN; higher ALP and calcium deposition; statistically significant effects (figures show p<0.05/p<0.01).
2. Al-Subaie AE et al., J Clin Periodontol 2016 — Propranolol enhances bone healing and implant osseointegration in rat tibiae.
In rats treated with propranolol (5 mg/kg): bone-implant contact increased from 42.5 ± 8.8% to 65.0 ± 13.1% (reported in the paper) and histology showed more new bone.
3. Tavakoli M et al., J Oral Maxillofac Res / PMC 2022 — Evaluating systemic administration effect of propranolol on bone-implant contact.
Osteoblasts and osteocytes express β₂-adrenergic receptors (β₂-ARs).
When activated by norepinephrine (NE) from sympathetic nerves:
1. β₂-AR → Gs protein → ↑ cAMP → activates PKA (protein kinase A).
2. PKA phosphorylates CREB and other transcription factors that suppress osteoblast differentiation and promote osteoclast activity.
3. Net result → bone resorption ↑, bone formation ↓.
Propranolol = non-selective β-blocker → inhibits this pathway.
---
2. Mechanistic sequence leading to BMP-2 increaseStep 1. β-blockade reduces cAMP/PKA signaling
Propranolol binds to β₁/β₂-ARs → prevents NE binding.
Intracellular cAMP levels fall → PKA activity decreases.
This changes transcriptional regulation in osteoblast lineage cells.
Evidence: Wu et al. (2021, Int J Mol Med) showed propranolol lowered cAMP and PKA levels in MSCs, correlating with BMP-2 and Runx2 upregulation.
These are the mechanisms behind this:
Relief of inhibitory CREB signaling and activation of osteogenic genes
Under high PKA/CREB signaling, osteogenesis-related genes (including BMP-2, Runx2) are repressed.
β-blockade reduces CREB phosphorylation → de-repression of BMP-2 transcription.
Mechanistic markers in papers: ↓ p-CREB, ↑ BMP-2 mRNA, ↑ Runx2 mRNA, ↑ ALP activity.
---
BMP-2 autocrine/paracrine loop triggers osteogenic differentiation
Once expressed, BMP-2 binds to BMP receptors (BMPR-I/II) on osteoblast precursors:
1. Activates SMAD1/5/8 phosphorylation.
2. SMAD complex with SMAD4 → translocates to nucleus.
3. Induces Runx2, Osterix, COL-1, OCN, ALP, etc.
→ drives osteoblast differentiation and matrix mineralization.
Supporting data: Propranolol-treated MSCs show ↑ p-SMAD1/5/8, ↑ Runx2, ↑ COL-1, ↑ OCN, and stronger Alizarin Red calcium staining.
---
Step 4. Secondary systemic mechanisms
(a) Reduced sympathetic tone → lower RANKL expression in osteoblasts)
Less RANKL → ↓ osteoclastogenesis → bone resorption suppressed.
Allows net anabolic balance favoring BMP-2-driven formation.
(b) Increased local perfusion / angiogenic coupling
Some studies note propranolol modulates VEGF and HIF-1α → indirectly enhances the bone-formation microenvironment.
Its effect on testosterone isn't something massive you might see a neutral or slight drop in testosterone but the effects are minimal and shouldn't be something to be worried about.
