PMID- 34934625
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231108
IS  - 2214-031X (Print)
IS  - 2214-0328 (Electronic)
IS  - 2214-031X (Linking)
VI  - 32
DP  - 2022 Jan
TI  - Kindlin-2 deletion in osteoprogenitors causes severe chondrodysplasia and 
      low-turnover osteopenia in mice.
PG  - 41-48
LID - 10.1016/j.jot.2021.08.005 [doi]
AB  - BACKGROUND: Our recent studies demonstrate that the focal adhesion protein 
      Kindlin-2 exerts crucial functions in the mesenchymal stem cells, mature 
      osteoblasts and osteocytes in control of early skeletal development and bone 
      homeostasis in mice. However, whether Kindlin-2 plays a role in osteoprogenitors 
      remains unclear. MATERIALS AND METHODS: Mice lacking Kindlin-2 expression in 
      osterix (Osx)-expressing cells (i.e., osteoprogenitors) were generated. 
      Micro-computerized tomography (muCT) analyses, histology, bone histomorphometry 
      and immunohistochemistry were performed to determine the effects of Kindlin-2 
      deletion on skeletal development and bone mass accrual and homeostasis. Bone 
      marrow stromal cells (BMSCs) from mutant mice (Kindlin-2 (fl/fl) ; Osx (Cre) ) 
      and control littermates were isolated and determined for their osteoblastic 
      differentiation capacity. RESULTS: Kindlin-2 was highly expressed in 
      osteoprogenitors during endochondral ossification. Deleting Kindlin-2 expression 
      in osteoprogenitors impaired both intramembranous and endochondral ossifications. 
      Mutant mice displayed multiple severe skeletal abnormalities, including 
      unmineralized fontanel, limb shortening and growth retardation. Deletion of 
      Kindlin-2 in osteoprogenitors impaired the growth plate development and largely 
      delayed formation of the secondary ossification center in the long bones. 
      Furthermore, adult mutant mice displayed a severe low-turnover osteopenia with a 
      dramatic decrease in bone formation which exceeded that in bone resorption. 
      Primary BMSCs isolated from mutant mice exhibited decreased osteoblastic 
      differentiation capacity. CONCLUSIONS: Our study demonstrates an essential role 
      of Kinlind-2 expression in osteoprogenitors in regulating skeletogenesis and bone 
      mass accrual and homeostasis in mice. THE TRANSLATIONAL POTENTIAL OF THIS 
      ARTICLE: This study reveals that Kindlin-2 through its expression in 
      osteoprogenitor cells controls chondrogenesis and bone mass. We may define a 
      novel therapeutic target for treatment of skeletal diseases, such as 
      chondrodysplasia and osteoporosis.
CI  - (c) 2021 The Authors.
FAU - Wu, Xiaohao
AU  - Wu X
AD  - Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease 
      Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of 
      Biochemistry, School of Medicine, Southern University of Science and Technology, 
      Shenzhen, 518055, China.
FAU - Qu, Minghao
AU  - Qu M
AD  - Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease 
      Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of 
      Biochemistry, School of Medicine, Southern University of Science and Technology, 
      Shenzhen, 518055, China.
FAU - Gong, Weiyuan
AU  - Gong W
AD  - Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease 
      Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of 
      Biochemistry, School of Medicine, Southern University of Science and Technology, 
      Shenzhen, 518055, China.
FAU - Zhou, Chunlei
AU  - Zhou C
AD  - Department of Medical Laboratory, Tianjin First Center Hospital, Tianjin Medical, 
      17 University, Tianjin, 300192, China.
FAU - Lai, Yumei
AU  - Lai Y
AD  - Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, 
      60612, USA.
FAU - Xiao, Guozhi
AU  - Xiao G
AD  - Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease 
      Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of 
      Biochemistry, School of Medicine, Southern University of Science and Technology, 
      Shenzhen, 518055, China.
LA  - eng
PT  - Journal Article
DEP - 20210927
PL  - Singapore
TA  - J Orthop Translat
JT  - Journal of orthopaedic translation
JID - 101625127
PMC - PMC8639803
OTO - NOTNLM
OT  - Chondrodysplasia
OT  - Kindlin-2
OT  - Low-turnover osteopenia
OT  - Osteoprogenitor
OT  - Skeletogenesis
COIS- The authors declare that they have no competing financial interest.
EDAT- 2021/12/23 06:00
MHDA- 2021/12/23 06:01
PMCR- 2021/09/27
CRDT- 2021/12/22 06:50
PHST- 2021/06/28 00:00 [received]
PHST- 2021/08/16 00:00 [revised]
PHST- 2021/08/18 00:00 [accepted]
PHST- 2021/12/22 06:50 [entrez]
PHST- 2021/12/23 06:00 [pubmed]
PHST- 2021/12/23 06:01 [medline]
PHST- 2021/09/27 00:00 [pmc-release]
AID - S2214-031X(21)00067-X [pii]
AID - 10.1016/j.jot.2021.08.005 [doi]
PST - epublish
SO  - J Orthop Translat. 2021 Sep 27;32:41-48. doi: 10.1016/j.jot.2021.08.005. 
      eCollection 2022 Jan.