Growth hormone-receptor disruption in mice reduces osteoarthritis and chondrocyte hypertrophy
Excessive growth hormone (GH) has been shown to promote joint degeneration in both preclinical and clinical studies. Little is known about the effect of disrupted GH or GH receptor (GHR) on joint health. The goal of this study is to investigate joint pathology in mice with either germline ( GHR -/-...
Saved in:
Published in: | GeroScience Vol. 46; no. 5; pp. 4895 - 4908 |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Cham
Springer International Publishing
03-06-2024
Springer Nature B.V |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Excessive growth hormone (GH) has been shown to promote joint degeneration in both preclinical and clinical studies. Little is known about the effect of disrupted GH or GH receptor (GHR) on joint health. The goal of this study is to investigate joint pathology in mice with either germline (
GHR
-/-
) or adult inducible (
iGHR
-/-
) GHR deficiency. Knee joints from male and female
GHR
-/-
and WT mice at 24 months of age were processed for histological analysis. Also, knee joints from male and female
iGHR
-/-
and WT mice at 22 months of age were scanned by micro-CT (μCT) for subchondral bone changes and characterized
via
histology for cartilage degeneration. Joint sections were also stained for the chondrocyte hypertrophy marker, COLX, and the cartilage degeneration marker, ADAMTS-5, using immunohistochemistry. Compared to WT mice,
GHR
-/-
mice had remarkably smooth articular joint surfaces and an even distribution of proteoglycan with no signs of degeneration. Quantitatively,
GHR
-/-
mice had lower OARSI and Mankin scores compared to WT controls. By contrast,
iGHR
-/-
mice were only moderately protected from developing aging-associated OA.
iGHR
-/-
mice had a significantly lower Mankin score compared to WT. However, Mankin scores were not significantly different between
iGHR
-/-
and WT when males and females were analyzed separately. OARSI scores did not differ significantly between WT and
iGHR
-/-
in either individual or combined sex analyses. Both
GHR
-/-
and
iGHR
-/-
mice had fewer COLX
+
hypertrophic chondrocytes compared to WT, while no significant difference was observed in ADAMTS-5 staining. Compared to WT, a significantly lower trabecular thickness in the subchondral bone was observed in the
iGHR
-/-
male mice but not in the female mice. However, there were no significant differences between WT and
iGHR
-/-
mice in the bone volume to total tissue volume (BV/TV), bone mineral density (BMD), and trabecular number in either sex. This study identified that both germline and adult-induced GHR deficiency protected mice from developing aging-associated OA with more effective protection in
GHR
-/-
mice. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2509-2723 2509-2715 2509-2723 |
DOI: | 10.1007/s11357-024-01230-z |