Matrix metalloproteinase-9 expression in alveolar extraction sockets of zoledronic acid-treated rats

David L. Basi, Pamela Hughes, Vivek Thumbigere-Math, Ma'Ann Sabino, Ami Mariash, Scott A. Lunos, Eric Jensen, Rajaram Gopalakrishnan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: The use of nitrogen-containing bisphosphonates (n-bis) is associated with necrosis of the jaws, also known as bisphosphonate-related osteonecrosis of the jaws (BRONJ); however, the pathophysiology is unknown. Matrix metalloproteinase-9 (MMP-9) expression is essential for normal bone healing and is also required for angiogenesis. N-bis alters MMP-9 expression in vitro and in vivo; therefore, we hypothesized that n-bis alters MMP-9 expression during oral wound healing after tooth extraction. Materials and Methods: A total accumulated dose of 2.25 mg/kg (n = 20) of Zoledronic acid (ZA) Zometa or saline (control, n = 20) was administered to SpragueDawley male rats. Next, both groups had maxillary molar teeth extracted. Rats were sacrificed at postoperative day 1, 3, 7, or 21. Western blotting or multiplex ELISA was used to evaluate proteins of interest. Real-time polymerase chain reaction was used to assess the relative quantities of target gene mRNA. MMP-9 enzymatic activity was assessed by zymography. Results: The ZA group showed a statistically significant reduction in bone mineralization rate 21 days after tooth extraction compared with the control group (Student t test, P =.005). Moreover, ZA-treated animals showed a statistically significant increase in MMP-9-specific mRNA at postoperative days 3 (P =.003), 7 (P .05). Receptor of NF-κB ligand (RANKL) is known to regulate the expression of MMP-9; we therefore assessed the RANKL expression in our experimental oral wound-healing model. The ZA-treated animals had significantly increased RANKL mRNA at postoperative days 3 (P =.02) and 21 (P =.004), while the protein expression was significantly increased at postoperative days 1 (P

Original languageEnglish (US)
Pages (from-to)2698-2707
Number of pages10
JournalJournal of Oral and Maxillofacial Surgery
Volume69
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

zoledronic acid
Matrix Metalloproteinase 9
Tooth Extraction
Diphosphonates
Wound Healing
Messenger RNA
Nitrogen
Bisphosphonate-Associated Osteonecrosis of the Jaw
Physiologic Calcification
Jaw
Real-Time Polymerase Chain Reaction
Tooth
Proteins
Necrosis
Western Blotting
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Oral Surgery
  • Otorhinolaryngology
  • Surgery

Cite this

Matrix metalloproteinase-9 expression in alveolar extraction sockets of zoledronic acid-treated rats. / Basi, David L.; Hughes, Pamela; Thumbigere-Math, Vivek; Sabino, Ma'Ann; Mariash, Ami; Lunos, Scott A.; Jensen, Eric; Gopalakrishnan, Rajaram.

In: Journal of Oral and Maxillofacial Surgery, Vol. 69, No. 11, 11.2011, p. 2698-2707.

Research output: Contribution to journalArticle

Basi, DL, Hughes, P, Thumbigere-Math, V, Sabino, MA, Mariash, A, Lunos, SA, Jensen, E & Gopalakrishnan, R 2011, 'Matrix metalloproteinase-9 expression in alveolar extraction sockets of zoledronic acid-treated rats', Journal of Oral and Maxillofacial Surgery, vol. 69, no. 11, pp. 2698-2707. https://doi.org/10.1016/j.joms.2011.02.065
Basi, David L. ; Hughes, Pamela ; Thumbigere-Math, Vivek ; Sabino, Ma'Ann ; Mariash, Ami ; Lunos, Scott A. ; Jensen, Eric ; Gopalakrishnan, Rajaram. / Matrix metalloproteinase-9 expression in alveolar extraction sockets of zoledronic acid-treated rats. In: Journal of Oral and Maxillofacial Surgery. 2011 ; Vol. 69, No. 11. pp. 2698-2707.
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AU - Basi, David L.

AU - Hughes, Pamela

AU - Thumbigere-Math, Vivek

AU - Sabino, Ma'Ann

AU - Mariash, Ami

AU - Lunos, Scott A.

AU - Jensen, Eric

AU - Gopalakrishnan, Rajaram

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N2 - Purpose: The use of nitrogen-containing bisphosphonates (n-bis) is associated with necrosis of the jaws, also known as bisphosphonate-related osteonecrosis of the jaws (BRONJ); however, the pathophysiology is unknown. Matrix metalloproteinase-9 (MMP-9) expression is essential for normal bone healing and is also required for angiogenesis. N-bis alters MMP-9 expression in vitro and in vivo; therefore, we hypothesized that n-bis alters MMP-9 expression during oral wound healing after tooth extraction. Materials and Methods: A total accumulated dose of 2.25 mg/kg (n = 20) of Zoledronic acid (ZA) Zometa or saline (control, n = 20) was administered to SpragueDawley male rats. Next, both groups had maxillary molar teeth extracted. Rats were sacrificed at postoperative day 1, 3, 7, or 21. Western blotting or multiplex ELISA was used to evaluate proteins of interest. Real-time polymerase chain reaction was used to assess the relative quantities of target gene mRNA. MMP-9 enzymatic activity was assessed by zymography. Results: The ZA group showed a statistically significant reduction in bone mineralization rate 21 days after tooth extraction compared with the control group (Student t test, P =.005). Moreover, ZA-treated animals showed a statistically significant increase in MMP-9-specific mRNA at postoperative days 3 (P =.003), 7 (P .05). Receptor of NF-κB ligand (RANKL) is known to regulate the expression of MMP-9; we therefore assessed the RANKL expression in our experimental oral wound-healing model. The ZA-treated animals had significantly increased RANKL mRNA at postoperative days 3 (P =.02) and 21 (P =.004), while the protein expression was significantly increased at postoperative days 1 (P

AB - Purpose: The use of nitrogen-containing bisphosphonates (n-bis) is associated with necrosis of the jaws, also known as bisphosphonate-related osteonecrosis of the jaws (BRONJ); however, the pathophysiology is unknown. Matrix metalloproteinase-9 (MMP-9) expression is essential for normal bone healing and is also required for angiogenesis. N-bis alters MMP-9 expression in vitro and in vivo; therefore, we hypothesized that n-bis alters MMP-9 expression during oral wound healing after tooth extraction. Materials and Methods: A total accumulated dose of 2.25 mg/kg (n = 20) of Zoledronic acid (ZA) Zometa or saline (control, n = 20) was administered to SpragueDawley male rats. Next, both groups had maxillary molar teeth extracted. Rats were sacrificed at postoperative day 1, 3, 7, or 21. Western blotting or multiplex ELISA was used to evaluate proteins of interest. Real-time polymerase chain reaction was used to assess the relative quantities of target gene mRNA. MMP-9 enzymatic activity was assessed by zymography. Results: The ZA group showed a statistically significant reduction in bone mineralization rate 21 days after tooth extraction compared with the control group (Student t test, P =.005). Moreover, ZA-treated animals showed a statistically significant increase in MMP-9-specific mRNA at postoperative days 3 (P =.003), 7 (P .05). Receptor of NF-κB ligand (RANKL) is known to regulate the expression of MMP-9; we therefore assessed the RANKL expression in our experimental oral wound-healing model. The ZA-treated animals had significantly increased RANKL mRNA at postoperative days 3 (P =.02) and 21 (P =.004), while the protein expression was significantly increased at postoperative days 1 (P

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