Utjecaj koštanih morfogenetskih proteina 2 i 7 na volumen kosti u štakora s uklonjenom štitnom i doštitnim žlijezdama

doctoral thesis

• Title (english): Effects of bone morphogenetic protein 2 and 7 on bone volume in rats with removed thyroid and parathyroid glands
• Author: Ivo Dumić-Čule
• Mentor: Lovorka Grgurević (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2016-07-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Koštani morfogenetski proteini (BMP)2 i 7 nakon niza kliničkih studija odobreni su od
strane FDA za liječenje kompliciranih fraktura tibije te za spinalnu fuziju. Nakon lokalne
ugradnje naprave s BMP2 ili 7 manja količina oslobađa se u sistemsku cirkulaciju.
Do sada izravni učinak oslobođenih molekula BMP2 i 7 na koštani metabolizam nije
istražen. Razvili smo štakorski model tireoparatireoidektomije (TPTx) sa smanjenom razinom
kalciotropnih hormona na kojem smo testirali sistemski učinak BMP2 i 7. Primjenjene doze
BMP2 i 7 određene su prema objavljenim rezultatima farmakodinamike i otpuštanja s mjesta
lokalne primjene.
TPTx operacija rezultirala je gubitkom koštanog volumena, koji je nadoknađen
primjenom 10-70 μg/kg BMP2 i 10-250 μg/kg BMP7. BMP2 kvalitetnije je nadoknadio broj
trabekula, dok je BMP7 prvenstveno djelovao da debljinu trabekula. In vitro eksperimenti
pokazali su da BMP2 i 7 povećavaju aktivnost i broj osteoblasta i osteoklasta kad stanice nisu
u međusobnoj interakciji.
BMP2 i 7 povećavaju koštani volumen u životinja bez kalciotropnih hormona, što
potvrđuje njihov izravan efekt. Zaključno, BMP2 i 7 koji se otpuste u sistemsku cirkulaciju
nakon lokalne implantacije neće uzrokovati gubitak koštanog volumena.

Abstract (english)

BMP2 and 7 are used locally in FDA approved indications including complicated long
bone fractures, non-unions, and spinal fusions. It is unknown whether their systemic release
following a local implantation might impact systemically the bone metabolism. Furthermore,
it is unknown whether systemic BMP effects on bone are direct or mediated by calciotropic
hormones.
Removal of thyroid and parathyroid glands (TPTx) in rats resulted in the decreased
level of calciotropic hormones and afterwards we initiated the treatment with BMP2 or 7. The
administered doses have been calculated according to published bioavailability data from preclinical
BMP2 and 7 studies. Additionally, BMP2 and 7 were tested in vitro to estimate their
influence on osteoblast and osteoclast activity.
TPTx resulted in bone loss which was restored by systemic administration of 10-70
μg/kg of BMP2 and all doses of BMP7. BMP2 showed a higher capacity for increasing
trabecular number, while BMP7 augmented trabecular thickness. In vitro experiments
revealed that BMP2 and 7, when uncoupled, increased the number and activity of both
osteoblasts and osteoclasts.
Collectively, locally administered BMP2 and 7 from bone devices might become
partially available in circulation but will not mediate a systemic bone loss.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:804336
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 75 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 07:57:33